Lecture 9_02-09-24.pdf

Introduction to Bioengineering (BBL1020) Instructor: Dr. Dinesh K. Ahirwar Department: Bioscience & Bioengineering Lecture-9 2/09/2024 Structure-activity relationship संरचना-ग)त+व-ध संबंध संरचना-ग)त+व-ध संबंध  Structure-activity re...

Introduction to Bioengineering (BBL1020) Instructor: Dr. Dinesh K. Ahirwar Department: Bioscience & Bioengineering Lecture-9 2/09/2024 Structure-activity relationship संरचना-ग)त+व-ध संबंध संरचना-ग)त+व-ध संबंध  Structure-activity relationship (SAR) Ø The structure-activity relationship is the relationship between the chemical structure of a molecule and its biological activity Ø First presented by Crum-Brown and Fraser in 1865 Ø Enables the determination of the chemical group (pharmacophores) responsible for evoking a target biological effect in the organism Ø Allows modification of the effect or the potency of a bioactive compound (typically a drug) by changing its chemical structure Ø To discover new drugs and also repurpose existing drugs – for the improvement in the biological activity Pharmacophore with their biological effects Hydroxyl group (-OH) Addition of (-OH) reduces biological activity of aliphatic compounds Example: Hexanal is more toxic than glucose CH3-(CH2)4-COH CH2OH-(CHOH)4-COH Propanol is more toxic than glycerol CH3-CH2-CH2-OH CH2—CH — CH2 OH OH OH Propanol Glycerol  Pharmacophore with their biological effects Addition of (-OH) increases the physiological activities of aromatic compound No-antiseptic antiseptic Pharmacophore with their biological effects Not an Antiseptic Antiseptic Pharmacophore with their biological effects Toxicity of the compound increases with increasing unsaturation Propanol is less toxic Allyl alcohol is poisonous Modification of parent compound Effect of amino group (-NH3) Amino group is toxic in nature Alkylation or acetylation reduces toxicity NHCHCO3 Febrifuge Acetylation reduces toxicity of aniline Acetanilide Think and answer Arrange the compounds in their increasing order of toxicity NH2 -NH 1 2 3 4 Barbiturate: a sedative medicine 2 1 3 6 4 5 H H Pyrimidine Hexahydropyrimidine 2,4,6 hydroxy hexahydropyrimidine Barbiturate  If you not connected to Please answer this wifi, raise your hand question in G-Forms Question: How will the addition of unsaturated alkyl chain of 3 carbons will affect bioactivity of Barbiturate? A. Will not affect B. Decrease C. Increase SAR of Barbiturate Addition of alkyl chain increases activity 2 Length of carbon chain increases bioactivity by 1 3 increasing lipophilic nature 6 4 5 Alkyl chain longer than 6 carbons decreases activity due to bulky structure H H 2,4,6 hydroxy Addition of phenyl group increases lipophilic hexahydropyrimidine activity many folds, hence will increase the Barbiturate bioactivity many folds  Addition of alkyl chain increases activity 2 Length of carbon chain increases bioactivity by 1 3 increasing lipophilic nature 6 4 5 Addition of too many alkyl chain will abolish activity, due to loss of water solubility H H 2,4,6 hydroxy hexahydropyrimidine Barbiturate  - Carl Neuberg (1908) - Altman and Cech (1989) - RNAs are information containing molecules just like DNA. - However, they have a secondary function which was discovered much later after their discovery. - OH groups present in their structure aid in their catalysis. 16