Kapnayan 2025 Medicinal Chemistry PDF

Overview of the History of Medicinal Chemistry Although the term “Medicinal Chemistry was coined after World War II, the use of chemicals for medicinal purposes has been documented tracing back to ancient times. Ancient people discovered that certain herbs and plants have therapeutic effects withou...

Overview of the History of Medicinal Chemistry Although the term “Medicinal Chemistry was coined after World War II, the use of chemicals for medicinal purposes has been documented tracing back to ancient times. Ancient people discovered that certain herbs and plants have therapeutic effects without understanding the mechanism of action of these plants on the human body. These plants and herbs have cultural significance to ancient people due to the belief they have magical and healing properties. Ancient China used herbs such as ginseng (Panax Ginseng) to treat a wide range of diseases such as shortness of breath and palpitations. (Maria Assunta Potenza et al., 2022). Ancient Egyptians and Sumerians used willow bark as a painkiller and antipyretic (Salix spp.) (Lin et al., 2023) During the Renaissance, Paracelsus pioneered alchemy to discover the use of chemicals for medicinal purposes such as inorganic compounds like mercury and antimony. This is the turning point of the primitive idea of “Active ingredients”. The French courts banned the use of chemistry for medicine until Louis XIV cured from chronic digestion using an antimony purge (Selina & Garneau-Tsodikova, 2017) During the early 1900s, modern medicinal chemistry was pioneered due to the discovery of many medical drugs. The discovery of Aspirin has marked the chemical synthesis for drug production since this is the first synthetic drug that has been widely used for pain relief (Maria Rosa Montinari et al., 2018). During World War I, due to the use of chemical warfare, this urged for significant research in chemical synthesis. In 1920, the first sulfa drugs were developed laying the groundwork for antibiotics then later in 1930, Prontosil was discovered by Gerhard Domagk, it is the first commercially available sulfonamide antibiotic. (Selina & Garneau-Tsodikova, 2017). During World War II, Alexander Fleming discovered penicillin in 1928, the mass production of this antibiotic revolutionized the treatment of severe and life-threatening bacterial infections saving millions of lives (Kalvaitis 2023). After World War II, modern medicinal chemistry continued to rise. Due to advancements in drug discoveries, we have developed many chemical (Synthetic and natural products that have been studied for their mechanism of action on the human body. Nowadays, drugs are not only limited to painkillers and antibiotics but also have a wide variety of uses such as hormonal drugs, contraceptives, antidepressants, antiviral and antineoplastics (Cancer Drugs). (Selina & Garneau-Tsodikova, 2017) ‌References: 1.​ Carroll, P., Dervan, A., McCarthy, C., Woods, I., Beirne, C., Harte, G., … & Flood, M. (2023). The role of patient and public involvement (ppi) in pre-clinical spinal cord research: an interview study.. https://doi.org/10.1101/2023.07.19.23292756 2.​ Chorniy, A., Bailey, J., Ci̇van, A., & Maloney, M. (2020). Regulatory review time and pharmaceutical research and development. Health Economics, 30(1), 113-128. https://doi.org/10.1002/hec.4180 3.​ Corneli, A., Dombeck, C., McKenna, K., & Calvert, S. (2021). Stakeholder experiences with the single irb review process and recommendations for food and drug administration guidance. Ethics & Human Research, 43(3), 26-36. https://doi.org/10.1002/eahr.500092 4.​ Costello, W. and Dorris, E. (2019). Laying the groundwork: building relationships for public and patient involvement in pre‐clinical paediatric research. Health Expectations, 23(1), 96-105. https://doi.org/10.1111/hex.12972 5.​ Damle, N., Shah, S., Nagraj, P., Tabrizi, P., Rodriguez, G., & Bhambri, R. (2017). Fda’s expedited programs and their impact on the availability of new therapies. Therapeutic Innovation & Regulatory Science, 51(1), 24-28. https://doi.org/10.1177/2168479016666587 6.​ Goodsaid, F. and Frueh, F. (2007). Implementing the u.s. fda guidance on pharmacogenomic data submissions. Environmental and Molecular Mutagenesis, 48(5), 354-358. https://doi.org/10.1002/em.20294 7.​ Joppi, R., Bertelè, V., Vannini, T., & Banzi, R. (2019). Food and drug administration vs european medicines agency: review times and clinical evidence on novel drugs at the time of approval. British Journal of Clinical Pharmacology, 86(1), 170-174. https://doi.org/10.1111/bcp.14130 8.​ Kanter, G., Vallurupalli, N., Xu, Y., & Gupta, R. (2021). Vaccine approvals and the role of the fda vaccine advisory committee, 2000-2019.. https://doi.org/10.1101/2021.07.19.21260761 9.​ Kern, K. (2016). Trial design and efficacy thresholds for granting breakthrough therapy designation in oncology. Journal of Oncology Practice, 12(8), e810-e817. https://doi.org/10.1200/jop.2016.012161 10.​ Kesselheim, A., Wang, B., Franklin, J., & Darrow, J. (2015). Trends in utilization of fda expedited drug development and approval programs, 1987-2014: cohort study. BMJ, h4633. https://doi.org/10.1136/bmj.h4633 11.​ Kumari, R. (2019). Bridging the gap between pre-clinical and clinical studies in cancer research. Novel Approaches in Cancer Study, 2(4). https://doi.org/10.31031/nacs.2019.02.000545 12.​ Maffini, M., Alger, H., Bongard, E., & Neltner, T. (2011). Enhancing fda's evaluation of science to ensure chemicals added to human food are safe: workshop proceedings. Comprehensive Reviews in Food Science and Food Safety, 10(6), 321-341. https://doi.org/10.1111/j.1541-4337.2011.00165.x 13.​ Maffini, M., Alger, H., Olson, E., & Neltner, T. (2013). Looking back to look forward: a review of fda's food additives safety assessment and recommendations for modernizing its program. Comprehensive Reviews in Food Science and Food Safety, 12(4), 439-453. https://doi.org/10.1111/1541-4337.12020 14.​ Olivencia, S. and Sasangohar, F. (2019). Investigating the food and drug administration biotherapeutics review and approval process: narrative review (preprint).. https://doi.org/10.2196/preprints.14563 15.​ Samuel, N. and Verma, S. (2016). Cross-comparison of cancer drug approvals at three international regulatory agencies. Current Oncology, 23(5), 454-460. https://doi.org/10.3747/co.23.2803 16.​ Simeon-Dubach, D., Zeisberger, S., & Hoerstrup, S. (2016). Quality assurance in biobanking for pre-clinical research. Transfusion Medicine and Hemotherapy, 43(5), 353-358. https://doi.org/10.1159/000448254 17.​ Souza, S., Johansson, E., Karlfeldt, S., Raza, K., & Williams, R. (2022). Patient and public involvement in an international rheumatology translational research project: an evaluation. BMC Rheumatology, 6(1). https://doi.org/10.1186/s41927-022-00311-w​ ​ Maria Assunta Potenza, Montagnani, M., Santacroce, L., Ioannis Alexandros Charitos, & Bottalico, L. (2022).  Ancient herbal therapy: A brief history of Panax ginseng. Journal of Ginseng Research, 47(3), 359–365. https://doi.org/10.1016/j.jgr.2022.03.004 18.​ ‌Lin, C.-R., Huang, S., Wang, C., Lee, C.-L., Hung, S.-W., Ting, Y.-T., & Yu Chiang Hung. (2023). Willow Bark (Salix spp.) Used for Pain Relief in Arthritis: A Meta-Analysis of Randomized Controlled Trials. Life, 13(10), 2058–2058. https://doi.org/10.3390/life13102058 19.​ ‌Selina, & Garneau-Tsodikova, S. (2017). What is medicinal chemistry? – Demystifying a rapidly evolving discipline! MedChemComm, 8(9), 1739–1741. https://doi.org/10.1039/c7md90030a 20.​ Maria Rosa Montinari, Minelli, S., & Raffaele De Caterina. (2018). The first 3500 years of aspirin history from its roots – A concise summary. Vascular Pharmacology, 113, 1–8. https://doi.org/10.1016/j.vph.2018.10.008 21.​ Kalvaitis (2023, October 2).Penicillin: An accidental discovery changed the course of medicine. Healio.com. https://www.healio.com/news/endocrinology/20120325/penicillin-an-accidental-discovery-changed-the-cours e-of-medicine Traditional Medicine Traditional medicine (TM) encompasses diverse health practices, knowledge, and beliefs rooted in indigenous cultures worldwide (Byadgi, 2014; Liao et al., 2020). It has been utilized for centuries, contributing significantly to primary healthcare, particularly at the community level (Byadgi, 2014). TM's popularity has surged globally since the 1990s, with increasing demand in both developed and developing countries (Byadgi, 2014; Liao et al., 2020). The richness of TM systems is often determined by the depth and length of a civilization's history, with Chinese, Indian, and Iranian medicines among the most comprehensive (Vessal, 2013). Traditional herbal medicine, a subset of TM, is widely applied in Asia, Africa, and Latin America (Liu, 2010). TM has contributed to modern medical science through the discovery of new medicines, such as ephedrine and artemisinin (Liao et al., 2020). In Western countries, adaptations of TM are often termed "complementary" or "alternative" medicine (Liu, 2010). Alternative Medicine Alternative medicine encompasses a wide range of practices and therapies that fall outside conventional medical approaches (Greenberg, 1999; Shakeel et al., 2011). These include folk medicine, herbal remedies, homeopathy, Ayurveda, chiropractic, acupuncture, and naturopathy, among others (Greenberg, 1999; Rao et al., 2021). The popularity of alternative medicine stems from its perceived compatibility with patients' values and beliefs, offering greater personal autonomy in healthcare decisions (Rao et al., 2021). Alternative therapies can be used either as substitutes for or in conjunction with standard medical treatments (Shakeel et al., 2011). The widespread acceptance of alternative medicine is attributed to its congruence with individuals' beliefs about health and illness (Rao et al., 2021). However, it's important to note that many alternative therapies may lack scientific explanations for their effectiveness (Shakeel et al., 2011). Despite this, alternative medicine continues to be widely used for treating various diseases and is increasingly recognized as a complementary approach to conventional healthcare (Rao et al., 2021). The Formulation of the First Antibiotics One of the most pivotal moments in medical history came in 1928 when Alexander Fleming discovered penicillin, the first true antibiotic. This discovery revolutionized medicine, providing an effective treatment for bacterial infections. Fleming’s accidental discovery, combined with the later work of scientists like Howard Florey and Ernst Boris Chain, led to the mass production of penicillin, which was especially vital during World War II. The First Vaccine The earliest known vaccine was developed by Edward Jenner in 1796 to combat smallpox. Jenner used material from cowpox lesions to create immunity against smallpox, setting the stage for the field of immunology. Jenner's work was groundbreaking, establishing the principle of vaccination by using a less harmful virus to stimulate immunity. Additional breakthroughs followed with Louis Pasteur, who developed vaccines for rabies and anthrax in the late 19th century. His contributions further solidified the idea of using attenuated (weakened) organisms to protect against more dangerous diseases. Major Breakthroughs The development of vaccines in the 20th century marked significant advancements in disease prevention. Following early bacterial vaccines in the 1900s, including those for diphtheria and tetanus (Baker & Katz, 2004), the 1950s saw a surge in viral vaccine development due to improved tissue culture techniques. This led to vaccines for polio, measles, mumps, rubella, and varicella (Baker & Katz, 2004; Hsu, 2013). The creation of inactivated (Salk) and live oral (Sabin) polio vaccines was particularly noteworthy, contributing to the near-eradication of polio globally (Ishmukhametov et al., 2019). The latter part of the century witnessed further innovations, utilizing new technologies to create vaccines for hepatitis B and Haemophilus influenzae type b (Baker & Katz, 2004). These advancements were made possible by evolving knowledge in microbiology, immunology, and molecular biology (Hsu, 2013; Plotkin, 2014), highlighting the crucial role of scientific progress in vaccine development throughout the 20th century. The COVID-19 Vaccine The development of COVID-19 vaccines has been crucial in combating the global pandemic caused by SARS-CoV-2 (Athavale, 2021). Various vaccine platforms, including gene-based and protein-based vaccines, have been utilized (Yadav et al., 2023). The BNT162b2 mRNA vaccine, developed by Pfizer-BioNTech, demonstrated 95% efficacy in preventing COVID-19 in a large-scale clinical trial (Polack et al., 2020). Vaccine rollout has been implemented in phases, prioritizing healthcare workers, elderly individuals, and those with underlying medical conditions (Fernandes et al., 2021). While most vaccines have shown local or systemic effects after administration, they have varied efficacy against SARS-CoV-2 and its variants (Yadav et al., 2023). The success of vaccination efforts depends not only on the availability of efficient vaccines but also on addressing vaccine hesitancy, training healthcare workers, and ensuring adequate vaccine coverage (Athavale, 2021). Continued research is necessary to refine vaccine technology, minimize adverse effects, and improve safety and efficacy (Yadav et al., 2023). ‌References: 1.​ Byadgi, Parmeswarappa Shivappa. "Traditional Medicines an Effective Tool in Health Care: To be Implemented in National Health Policy." Journal of Advanced Research in Ayurveda, Yoga, & Homeopathy 1, no. 1 (2014): 1-2. 2.​ ‌Vessal, Karim. “Traditional medicine: a historical appraisal.” Archives of Iranian medicine 16 12 (2013): 696.  3.​ Liao, F.; Jiang, T.; Tu, Y. Traditional Medicine Exemplified by Traditional Chinese Medicine. Oxford University Press eBooks 2020, 108-C2.8.P43. https://doi.org/10.1093/med/9780198746690.003.0014. 4.​ ‌Liu, W. J. H. Introduction to Traditional Herbal Medicines and Their Study. Traditional Herbal Medicine Research Methods 2010, 1–26. https://doi.org/10.1002/9780470921340.ch1. 5.​ ‌Fleming, Alexander. "On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae." British journal of experimental pathology 10, no. 3 (1929): 226. 6.​ Alexander Fleming Discovery and Development of Penicillin - Landmark. American Chemical Society. https://www.acs.org/education/whatischemistry/landmarks/flemingpenicillin.html#citation 7.​ The college of Physicians of Philadelphia. Edward Jenner, FRS FRCPE. cpp-hov.netlify.app. https://historyofvaccines.org/history/edward-jenner-frs-frcpe/overview. 8.​ Louis Pasteur, ForMemRS. cpp-hov.netlify.app. https://historyofvaccines.org/history/louis-pasteur-formemrs/overview. 9.​ Vaccine Timeline. cpp-hov.netlify.app. https://historyofvaccines.org/history/vaccine-timeline/timeline. 10.​ ‌ALTERNATIVE MEDICINE: THERAPIES and TREAT the DISEASES by NEW WAYS. International Research Journal of Modernization in Engineering Technology and Science 2023. https://doi.org/10.56726/irjmets33003. 11.​ ‌Greenberg, S. Alternative Medicine and the Internet. Paediatrics & Child Health 1999, 4 (8), 539–541. https://doi.org/10.1093/pch/4.8.539. 12.​ ‌Shakeel, Memon, Pathan Dilnawaz, Ziyaurrrahman, Kamal Safura and Bora Chanderprakash. “ALTERNATIVE SYSTEM OF MEDICINE IN INDIA : A REVIEW.” International research journal of pharmacy 2 (2011): 29-37. 13.​ RAO, M. T.; YAMINI, M.; PHANINDRA, CVS.; RAO, Y. S. Alternative Medicine: New Ways to Treat Diseases and Therapies. Indian Journal of Pharmaceutical Sciences 2021, 83 (1). https://doi.org/10.36468/pharmaceutical-sciences.744. 14.​ Hsu, Jennifer L. “A brief history of vaccines: smallpox to the present.” South Dakota medicine : the journal of the South Dakota State Medical Association Spec no (2013): 33-7. 15.​ A.A. Ishmukhametov; A.A. Siniugina; K.M. Chumakov. The Development of Polio Vaccines: The Current Update (Review). Sovremennye tehnologii v medicine 2019, 11 (4), 200–200. https://doi.org/10.17691/stm2019.11.4.22. 16.​ ‌Baker, J. P.; Katz, S. L. Childhood Vaccine Development: An Overview. Pediatric Research 2004, 55 (2), 347–356. https://doi.org/10.1203/01.pdr.0000106317.36875.6a. 17.​ ‌Plotkin, S. History of Vaccination. Proceedings of the National Academy of Sciences 2014, 111 (34), 12283–12287. https://doi.org/10.1073/pnas.1400472111. 18.​ ‌Jonas Salk, MD. cpp-hov.netlify.app. https://historyofvaccines.org/history/jonas-salk-md/overview (accessed 2022-06-02). 19.​ ‌Athavale, A. V. The Covid-19 Vaccine. Journal of Advanced Research in Medical Science & Technology 2021, 08 (01), 29–35. https://doi.org/10.24321/2394.6539.202103. 20.​ ‌Yadav, T.; Kumar, S.; Mishra, G.; Saxena, S. K. Tracking the COVID-19 Vaccines: The Global Landscape. Human Vaccines & Immunotherapeutics 2023. https://doi.org/10.1080/21645515.2023.2191577. 21.​ ‌Fernandes, A.; Chaudhari, S.; Jamil, N.; Gopalakrishnan, G. COVID-19 Vaccine Commentary. Endocrine Practice 2021. https://doi.org/10.1016/j.eprac.2021.01.013. 22.​ ‌(1)Polack, F. P.; Thomas, S. J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J. L.; Pérez Marc, G.; Moreira, E. D.; Zerbini, C.; Bailey, R.; Swanson, K. A.; Roychoudhury, S.; Koury, K.; Li, P.; Kalina, W. V.; Cooper, D.; Frenck, R. W.; Hammitt, L. L.; Türeci, Ö. Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine. New England Journal of Medicine 2020, 383 (27), 2603–2615. https://doi.org/10.1056/nejmoa2034577. Hit Compounds ​ Most compounds that are used in the pharmaceutical industry are based on compounds found in different organisms. Hit compounds refer to compounds that are desired due to their specific bioactivity. The determination of these compounds are done through multiple trials and screenings which can be done in a laboratory setting. The discovery of these compounds is another story. Common avenues of discovery for these compounds are through the use of texts from history as these record the ways people back then used certain plants to treat certain ailments. A good example of this would be artemisinin which is among the most recent plant-based drugs in the market (Thomas, 2021). Artemisinin is among one of the most influential drugs in recent history as it and its derivatives have made strides in the fight against malaria (Wang et.al., 2019). The discovery of this compound was through ancient Chinese literature where the plant (A. annua) was singled out due to its frequency in texts for recipes that were used against fever. Professor Youyou Tu had read a recipe regarding the extraction of a “juice” that was very effective against fever and she had determined that the extraction method was the main issue as it degraded most of the artemisinin in the extract. This discovery led to the determination of the artemisinin and her winning a Nobel Peace Prize in Physiology for her contributions in the discovery of artemisinin (Miller & Su, 2015). Another example of a hit compound would ɑ-Mangostin which from the name of the compound itself can be deduced to be from the Mangosteen tree. This compound was first discovered in 1855 from the Mangosteen tree (Meah et.al., 2024). The ɑ-Mangostin is a naturally occurring xanthonoid that can be extracted from the bark of the Mangosteen tree (Dey et.al., 2020). The significance of the compound is that it is very effective against Dengue virus infection as it is able to hinder viral load to an acceptable level and hinder the massive production of cytokine (Tarasuk et.al., 2017). This type of hit compound is able to answer two problems presented by the Dengue virus which makes it all the more sought after for drug development. References 1.​ Thomas, L. (2021). Plant-Based Drugs and Medicines. News Medical Life Sciences. Retrieved from: https://www.news-medical.net/health/Plant-Based-Drugs-and-Medicines.aspx 2.​ Wang, J., Xu, C., Wong Y.K., Li, Y., Liao, F., Jiang, T., & Tu, Y. (2019). Artemisinin, The Magic Drug Discovered from Traditional Chinese Medicine. Engineering. Elsevier. p32-39. https://doi.org/10.1016/j.eng.2018.11.011 3.​ Su, X. & Miller, L. (2015). The discovery of artemisinin and Nobel Prize in Physiology or Medicine. Sci. China Life Sci. doi: 10.1007/s11427-015-4948-7 4.​ Meah, M.S., Panichayupakaranant, P., Sayeed, M.A., & Kim, M.G. (2024). Isolation and Pharmacochemistry of α-Mangostin as a Chemotherapeutic Agent. Pharmacognosy Magazine. Sage Journals. https://doi.org/10.1177/09731296241262567 5.​ Dey, A., Nanda, B., Nandy, S., Mukherjee, A., & Pandey, D.K. (2020). Chapter 2- Implications of phytochemicals as disease-modifying agent against Huntington’s Disease (HD): Bioactivity, animal models  and transgenics, synergism and structure-activity studies. Studies in Natural Products Chemistry. Elsevier. https://doi.org/10.1016/B978-0-12-819483-6.00002-3 6.​ Tarasuk, M., Songprakhon, P., Chimma, P., Sratongno, P., Na-Bangchang, K., Yenchitsomanus, P., (2017). Alpha-mangostin inhibits both dengue virus production and cytokine/chemokine expression. Virus Research. Elsevier. https://doi.org/10.1016/j.virusres.2017.08.011 Graphical presentation about how the vaccines against diseases such as polio, measles, and tetanus, substantially reduce their prevalence and save countless lives. Figure 1. Global Trends in Reported Paralytic Polio Cases (1980–2023) The introduction of the Oral Polio Vaccine in the late 20th century was a pivotal moment in global health, leading to a drastic reduction in cases. Starting from over 52,630 reported cases in 1980, polio incidence dropped to fewer than 1,000 by the early 2000s, this is through the help of initiatives like the Global Polio Eradication Initiative launched in 1988 (Ochmann et al., 2017).  Figure 2. Incidence of Reported Measles Cases Globally (1980–2022) In 1981, the incidence of measles reached an all-time high, with over 4 million cases; in recent years, however, with the widespread use of the MMR vaccine, its incidence has drastically reduced. Periodic outbreaks throughout the late 1980s and mid-2000s were contained through vaccination programs, but otherwise, measles has generally been held at bay, with these vaccination programs saving thousands of lives (WHO, 2023; World Health Organization, 2024). Figure 3. Reported Global Tetanus Cases (1980–2022) Tetanus remains a significant public health issue due to its environmental nature, but widespread vaccination has dramatically decreased the number of cases, from over 110,000 in 1980 to fewer than 10,000 by 2021. Continued vaccination efforts are crucial, particularly in regions with limited healthcare access, to maintain control over this life-threatening disease (Behrens et al., 2017). Figure 4. Superimposed Trends in Global Polio, Measles, and Tetanus Cases (1980–2023) This figure shows the global impact of vaccination programs on polio, measles, and tetanus. Polio's decline was the most rapid and linear, but all three have gone down dramatically. Measles has periodic outbreaks, while tetanus, an environmentally persistent disease, still went down. The comparison clearly indicates the contribution that vaccination programs make toward reducing the global burden of the respective conditions and toward improving the living standards of people (Ochmann et al., 2017; Behrens et al., 2017; World Health Organization, 2024). References 1.​ Behrens, H., Ochmann, S., & Roser, M. (2017). Tetanus. Our World in Data; Our world in Data. https://ourworldindata.org/tetanus 2.​ Ochmann, S., Roser, M., Dattani, S., & Spooner, F. (2017, November 9). Polio. Our World in Data; Global Change Data Lab. https://ourworldindata.org/polio  3.​ WHO. (2023). History of Measles Vaccination. Www.who.int; World Health Organization. https://www.who.int/news-room/spotlight/history-of-vaccination/history-of-measles-vaccination 4.​ World Health Organization. (2024, January 3). Reported cases of measles. Our World in Data. https://ourworldindata.org/grapher/reported-cases-of-measles?tab=chart Current Government Project on Pharmaceutical and Drug Discovery Sector of the Philippines In March 2024, the Philippine Economic Zone Authority (PEZA) and the Food and Drug Administration (FDA) began collaborating with the Office of the Special Assistant to the President for Investment and Economic Affairs (OSAPIEA). Their goal is to enhance the country's pharmaceutical and medical device manufacturing capabilities by establishing specialized pharmaceutical economic zones. One of their intended tasks is to streamline the production of medicine, to attract more investors and stakeholders. This encourages the market to support local producers in expanding research and development, to increase the manufacturing capacity, and to ultimately lower the drug costs for the public. By adapting practices from ASEAN countries, the project supports businesses, creating over 19,000 jobs and generating PhP 25.489 billion in investments as of December 2023. These firms include Terumo, Arkray Industry, and Royale Life Pharma. (Department of Trade and Industry, 2024) Along with the establishment of pharmaceutical economic zones, the ‘Tuklas Lunas Program’ is another key project by the Philippine government. Led by the Department of Science and Technology (DOST) in partnership with the Philippine Council for Health Research and Development (PCHRD), the program seeks to harness the Philippines’ rich biodiversity and local expertise to produce high-quality medicines. The project aligns with the National Unified Health Research Agenda (2017-2022), which emphasizes the use of natural products for drug development, with the Philippines’ particular focus on terrestrial and marine species found in the country. These potential products can range from herbal supplements to full-fledged medicines, with a primary goal of addressing diseases that are prevalent in the Philippines. The program is not only advancing local drug discovery and development but also promoting self-reliance in healthcare by utilizing local knowledge and resources. (Gonzalez, 2019; Philippine Council for Health and Research Development, 2018) A key component of the Tuklas Lunas Program is its collaboration with Tuklas Lunas Centers (TLCs), which are located in various regions across the country. These centers focus on researching the natural resources available in their specific areas, studying the potential of local medicinal plants and other natural products. By working with 29 partner institutions nationwide, the program supports various stages of the drug discovery process, including both preclinical and clinical trials. They aim to promote healthcare independence by reducing reliance on imported drugs and ensuring more accessible, locally-developed treatments for Filipinos. (Philippine Council for Health and Research, 2022; Business Mirror, 2024) References: Department of Trade and Industry. (2024). PEZA and FDA join forces to establish pharmaceutical economic zones. Retrieved from https://www.dti.gov.ph/archives/news-archives/peza-fda-join-forces-establish-pharmaceutical-economic-zones/ Gonzalez, C. J. (2019, November 4). DOST-PCHRD pursues partnership with PH pharma industry on drug discovery. PNHRS. https://www.healthresearch.ph/index.php/news/668-dost-pchrd-pursues-partnership-with-ph-pharma-industry-on-d rug-discovery Philippine Council for Health Research and Development. (2018). TUKLAS LUNAS: The Philippine Drug Discovery and Development Program. https://www.healthresearch.ph › 222-technologies Philippine Council for Health Research and Development. (2022, April 5). Tuklas Lunas Centers - Philippine Council for Health Research and Development. https://www.pchrd.dost.gov.ph/funded-projects/tuklas-lunas-centers/ Business Mirror. (2024, September 8). DOST strengthens partnerships in local drug discovery, development | BusinessMirror. https://businessmirror.com.ph/2024/09/08/dost-strengthens-partnerships-in-local-drug-discovery-development/ One of the main drivers of the “triple threat” is the lack of access to affordable generic drugs in the Philippines, despite having access to healthcare One of the key drivers of the “triple threat” of health concerns in the Philippines is the limited access to affordable generic drugs. Despite the government’s efforts to make healthcare more accessible, many Filipinos still struggle with the high cost of medicines. This issue is particularly common in rural areas where drug availability is limited, and even when generic brands are available, their prices are sometimes still too high for many low-income households. (Lambojon et. al, 2020) Generic drugs can offer significant cost savings, their availability in public health facilities remains inconsistent due to its increased demand (Magno, 2022). This challenges many Filipino patients who rely on these medications to manage their health needs. With the limited supply of generic drugs, some Filipinos resort to purchasing the more expensive brand alternative, and if they cannot afford this option, they choose to forgo their medication altogether (Yee, 2019). This impacts the patients’ health in the long run as skipping medication worsens their health condition and lead to more severe health complications. References: Lambojon, K., Chang, J., Saeed, A., Hayat, K., Li, P., Jiang, M., Atif, N., Desalegn, G. K., Khan, F. U., & Fang, Y. (2020). Prices, Availability and Affordability of Medicines with Value-Added Tax Exemption: A Cross-Sectional Survey in the Philippines. International Journal of Environmental Research and Public Health, 17(14), 5242. https://doi.org/10.3390/ijerph17145242 Magno, C. (2022). Pharmaceutical Competition in the Philippines. Philippine Competition Commission. https://www.phcc.gov.ph/wp-content/uploads/2022/11/DP-2022-01-Pharmaceutical-Competition-in-the-Philippines.p df Yee, J. (2019, December 6). 99 percent of Filipinos can’t afford‍ prescription drugs, says survey. INQUIRER.net. https://newsinfo.inquirer.net/1198647/99-percent-of-filipinos-cant-afford%E2%80%8D-prescription-drugs-says-survey Antimicrobial Resistance Antibiotics are a pillar of modern medicine (Aljeldah, 2022) that has revolutionized the approach to combat infections, fatal diseases, and the emergence of bacteria in the human biome. Dating back to Alexander Fleming’s penicillin, developing antibiotics to respond to new viruses has constantly evolved throughout the years, from battling the common cold, to treating pneumonia, to an epidemic-birthing virus such as COVID-19. However, the advancement of pharmaceutical sciences and its usage is inevitably accompanied by the evolution of antimicrobial resistance (AMR), a phenomenon posing a significant global threat to public health and economies that has been escalating in recent years, but has existed for as long as antibiotics have existed (Fukuda, 2013; Aljeldah 2022), calling for the emergent need to discover new drugs. The misuse and overuse of antimicrobials in healthcare, agriculture, and industry have contributed to the emergence and spread of resistant microbes across various environmental niches, including the human microbiome (Brinkac et. al. 2017; Fukuda, 2013). Fleming’s Nobel Prize speech is often cited for his caution that “it is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them… there is the danger that the ignorant man may easily under-dose himself and, by exposing his microbes to nonlethal quantities of the drug, make them resistant.” (Fleming, 1945). True enough, microbes are found to eventually develop several mechanisms to overcome antibiotics. The most common mechanism is through mutation, where random changes in the genetic material of microorganisms confer to antibiotics, making them resistant. Microbes develop physiological mechanisms like permeability changes, target site inactivation, enzymatic modification, and acquisition of alternative pathways to lower their susceptibility to antibiotics (Aljeldah 2022). Another mechanism is gene transfer, whereby microorganisms exchange genetic material through plasmids, transposons, and integrons, allowing them to acquire multiple resistance genes from other resistant organisms in a single event (McDermott et. al., 2003). These naturally occurring mechanisms, in addition to improper intake and prescription of antibiotics, all add to the AMR crisis (Aljeldah 2022). Arguably, the threat of AMR is even more pressing than the emergence of new viruses, fungi, and bacteria. While viruses like the Ebola and COVID-19 can cause significant outbreaks and mortality, they can be mitigated through public health measures as well as the development of vaccines and treatments through scientific methods. Antimicrobial resistance, on the other hand, is a silent, insidious threat that is degrading our ability to treat common infections. In fact, the World Economic Forum in January 2013 warned that antibiotic resistance was one of the most serious global risks humanity must solve. The World Health Organization (WHO) estimated that AMR was a contributor to 4.95 million mortalities and is directly responsible for 1.27 million global deaths in 2019. To this day, AMR’s prevalence continues to increase rapidly. Just three years after Fleming’s Nobel Prize speech, 38% of Staphylococcus aureus strains in a London hospital were found to be penicillin-resistant (Barber & Rozwadowska-Dowzenko, 1948). Today, more than 2.8 million antimicrobial-resistant infections occur each year, in the US alone, with 35,000 resulting in mortalities (CDC AMR Threats Report, 2019). The occurrence of AMR-related deaths in the European Union (EU) was documented to be around 33,000/year, with healthcare costs amounting to about 1.5 billion/year (The European Commission, n.d.). Beyond that, the surge of AMR flags concerns on what it would mean for the effectiveness and safety of several medical practices in disease treatment. Antimicrobial resistance is a “catastrophic threat” that unless suppressed, the UK’s Chief Medical Officer recalls “We will find ourselves in a health system not dissimilar to the early 19th century,” a period void of antibiotics, thus making bacterial infections a life-threatening concern in organ transplants, chemotherapy, and even minor surgeries. Efforts to combat AMR are underway in some Western nations to accelerate the innovation of desperately needed novel antibiotics. To name a few, AMR Action Fund, Innovative Medicines Initiative (IMI), and CARB-X established by Boston University are projects and organizations that provide funding and support for antimicrobial research and development. But as microbes continue to evolve and with it, the continuance of AMR prevalence, the search for new novel antimicrobial agents will be a desperate demand for the years to come. References: Aljeldah, M. (2022, August 1). Antimicrobial resistance and its spread is a global threat. Antibiotics 2022, 11 (8), 1082. https://doi.org/10.3390/antibiotics11081082. Brinkac, L.; Voorhies, A.; Gomez, A.; Nelson, K. E. (2017, May 11). The threat of antimicrobial resistance on the human microbiome. Microbial Ecology 2017, 74 (4), 1001–1008. https://doi.org/10.1007/s00248-017-0985-z. Fukuda, K. (2013, May 1). Antimicrobial drug resistance threat: our duty towards future generations. Eastern Mediterranean Health Journal 2013, 19 (5), 399. https://doi.org/10.26719/2013.19.5.399. Huttner, A.; Harbarth, S.; Carlet, J.; Cosgrove, S.; Goossens, H.; Holmes, A.; Jarlier, V.; Voss, A.; Pittet, D. (2013, November 18). Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum. Antimicrobial Resistance and Infection Control 2013, 2 (1). https://doi.org/10.1186/2047-2994-2-31. Salam, Md. A.; Al-Amin, Md. Y.; Salam, M. T.; Pawar, J. S.; Akhter, N.; Rabaan, A. A.; Alqumber, M. a. A. (2023, July 1). Antimicrobial resistance: a growing serious threat for global public health. Healthcare 2023, 11 (13), 1946. https://doi.org/10.3390/healthcare11131946. Fleming A. (1945, December 11). Penicillin. Nobel Lecture, December 11, 1945. Retrieved 2024-10-19 from: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf Barber, M.; Rozwadowska-dowzenko, M. (1949, May 22). Infection by penicillin resistant staphyloeoeci. Lanclet, 1948 Vol. 255, 641-644. https://www.cabidigitallibrary.org/doi/full/10.5555/19492200614 World Health Organization: WHO. Antimicrobial resistance. Retrieved 2024-10-19 from: https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance. World Economic Forum. (2013). Global Risks 2013 Eight Edition. https://www3.weforum.org/docs/WEF_GlobalRisks_Report_2013.pdf U.S. Centers for Disease Control and Prevention. (2019). 2019 Antibiotic Resistance Threats Report. Retrieved 2024-10-20 from: https://www.cdc.gov/antimicrobial-resistance/data-research/threats/index.html European Commission. Public Health. EU Action on Antimicrobial Resistance. Retrieved 2024-10-20 from: https://ec.europa.eu/health/antimicrobial-resistance/eu-action-antimicrobial-resistance_en “The health inequity in the Philippines is aggravated by heavy reliance on imported raw materials for drug manufacturing, leading to inflated prices compared to neighboring countries. With most pharmaceutical products being imported from the United Stated, India, and Germany, total imports reached 2.7 billion U.S. dollars in 2022.” (Statista, 2023) Reliance on imported raw materials is a major driver of pharmaceutical inflation in the Philippines, heightening the existing health inequities in the country: disparities in affordability and access to healthcare. This dependence has led to inflated drug prices compared to neighboring countries, making essential medications inaccessible to many Filipinos. With the majority of pharmaceutical products being imported from foreign countries such as the United States, India, and Germany, total imports reached a staggering 2.7 billion U.S. dollars in 2022 (Statista, 2023), increasing the production cost of many essential medications and in turn, its market selling price. The country’s pharmaceutical inflation rate of 10.1% drives the increased medication and health services costs in the country, potentially making healthcare unsustainable for many individuals (Anam Raven et.al., 2022). Insulin and other maintenance medications are expected to increase in price (Anam Raven et.al., 2022). This presents significant challenges for the Philippine healthcare system, as many Filipinos struggle to afford necessary medications and health services which forces them to delay or accept inadequate treatment that will ultimately worsen the state of their health. This is particularly concerning for Indigenous Peoples (IPs) who experience serious cases of malnutrition, micronutrient deficiencies, and limited food supply compared to non-IPs (Duante et al., 2022). Moreover, reliance on imported drugs makes the Philippine pharmaceutical industry vulnerable to a shortage of medication in the event that disruptions in the global supply chain ensue. Additionally, lack of domestic drug manufacturers limits the country’s ability to respond to public health emergencies, causing further hardship for patients. Shortage of medical supplies may possibly drive its prices even further as what occurred during the COVID-19 pandemic. This inflation, coupled with the scarcity of medicines in both public and private sectors, unjustly affects the most vulnerable sectors in society: the marginalized communities with limited financial resources, aggravating the already existing gaps between the rich and poor in healthcare access. References: Statista. (2023, December 21). Topic: Pharmaceutical market in the Philippines. https://www.statista.com/topics/7369/pharmaceutical-market-in-the-philippines/ Anam, R.; Arias, C.; Benga, L.; Musong, C.; Vadil, Z.; Faller, E. (2022, December). The Impact of the Inflation Crisis in Medication Pricing in Asean Countries: A Review. International Journal of Research Publication and Reviews, Vo. 3 no 12, pp 1428-1435. https://ijrpr.com/uploads/V3ISSUE12/IJRPR8740.pdf Duante, C.; Austria, R.; Ducay, A.; Acuin, C.; Capanzana, M. (2022, February). Nutrition and Health Status of Indigenous Peoples (IPs) in the Philippines: Results of the 2013 National Nutrition Survey and 2015 Updating Survey. Philippine Journal of Science 151(1):513-531, 2022. https://philjournalsci.dost.gov.ph/images/pdf/pjs_pdf/vol151no1/nutrition_and_health_status_of_indigenous_p eople_in_the_Philippines_.pdf