Plants, Pharmaceuticals and Medicine PDF

CHEMISTRY 101 Major groups of secondary metabolites found in plants ‐ Phenolics ‐ Terpenoids ‐ Sulfur compounds ‐ Alkaloids and other nitrogen compounds ‐ Gums and mucilages Basic structure of major groups Biological activity of secondary metabolites Major groups of secondary...

CHEMISTRY 101 Major groups of secondary metabolites found in plants ‐ Phenolics ‐ Terpenoids ‐ Sulfur compounds ‐ Alkaloids and other nitrogen compounds ‐ Gums and mucilages Basic structure of major groups Biological activity of secondary metabolites Major groups of secondary metabolites found in plants Plant secondary metabolites can be divided into four major groups based on chemical structure. Overlap of medicinal compounds with primary metabolites can result in more groups, e.g., gums and mucilage. Phenolics: characterized by the presence of an aromatic ring plus one or more hydroxyl hydroxybenzoic substituents. acid Terpenoids and steroids: are formed by the linking together of a number of five carbon isoprene units. isoprene Alkaloids and other nitrogen containing compounds: all alkaloids are basic, nitogen‐ coniine containing substances with a nitrogen atom as a member of the ring system. Sulfur containing compounds: usually enzymatically release strong smelling volatile sulfur compounds. allicin  Basic structure of major groups Biological activity of secondary metabolites Phenolics Chemical class # of structures Occurrence Biological activity Phenolics Phenols 200 Universal in leaf + Antimicrobial other tissues Flavonoids 4000 Universal in Often pigments vascular plants Quinones 800 Widespread in Pigments higher plants Tannins indefinite Widespread in Bind to proteins plants Lignins indefinite Universal in Indigestible to vascular plants animals Flavonoids: Found almost universally as water‐soluble pigments. Different types distinguished such as; flavones, flavonols, flavanones, chalcones, anthocyanidins. Medicinal properties include ability to strengthening vasculature, anti‐ inflammatory, anti‐oxidant, anti allergic, antibacterial and antiviral effects. Quinones: Are oxidized and have –O in place of –OH Various types distinguished, e.g., napthoquinones (two aromatic rings) and anthraquinones (three aromatic rings). Have antibacterial and antifungal activity. Tannins: Polyphenolic macromolecules, bitter taste, and astringent, complex with proteins. Hydrolysable tannins consist of one or more sugars bonded to phenolic acid molecules; condensed tannins (proanthocyanidins) are made up of two or more flavonoid units which break down into anthocyanidins when treated with acids or high temperature. Ability to complex contributes to antiseptic effects (detoxify). Often used to treat diarrhea.  Terpenoids Chemical class # of structures Occurrence Biological activity Terpenoids Monoterpenes 1000 Widespread in Aromatic, essential oils antimicrobial Sesquiterpenes 1500 Asteraceae Bitter, toxic, Sesquiterpene allergenic lactones Diterpenes 2000 Common in latex Toxic, and resins allergenic Triterpenes and 100 + plant Widely distributed Various steroids sterols Saponins 600 70+ plant families Surfactants, (no gymnosperms) haemolytic Others: 90 000+ widespread Various tetraterpenes polyterpenes iridoids Monoterpenes: two isoprene units linked together. These are commonly known as the essential oils, e.g., clove oil. Sesquiterpenes and sesquiterpene lactones – three isoprene units, i.e., 15 C (sesquiterpenes) and sesquiterpenes with a lactone ring. Helenalin found in Arnica sp. Triterpenes have a framework of approximately 30 C. Many are medicinally important. Steroids are biogenetically derived from C30 precursors with some secondary modifications such that the number of isoprene units is not always obvious. All of them have the so called steroid skeleton, e.g. diosgenin Saponins are glycosides of triterpenes that are amphipathic. Broadly distributed in the plant kingdom. Often used as precursors in the synthesis of human hormones because of their structural similarity to human steroids. Cardiac glycosides are a group of steroidal glycosides named for their potent effect on the heart. Two types: cardenolides – five‐member ring above the basic steroidal skeleton and bufadienolides – six member ring above the steroid skeleton. Tetraterpenes are large 40C, highly lipohilic compounds, membrane associated, with antioxidant properties e.g., carotene. Polyterpenes: very large molecules (10 to 1000 isoprene units) common in latex. Iridoids: a specifc class of monoterpenes with the so called iridane skeleton that may be modified in various ways, e.g. harpogoside (Harpagophytumn procumbens). Terpenes (mono, sesqui, di, and tri) have a number of common activities. Highly hydrophobic and readily interact with membranes. increase fluidity leading to uncontrolled efflux of ions and metabolites, can lead to cell death by leakage. conformational changes in membrane proteins (e.g., channels and transporters) are possible when the terpenes penetrate membrane and accumulate close to proteins. if Na+, K+ or Ca++ channels are affected disturbances in signal transduction are possible. Membrane activity is unspecific thus terpenes can show antimicrobial and cytotoxic effects against a wide range of organisms (bacteria, fungi, insect, and vertebrates). Important functional groups of the terpenes are Aldehydes: form covalent bonds with free amino groups of proteins Terminal exocyclic methylene groups that couple to SH groups of proteins Inner oxides or peroxides of terpenes are chemically reactive and can bind to proteins. Geranial Camphor Eucalyptol Changes spatial structure and thus activity of the proteins. Side effects/toxicity of terpenes explained by same biological interactions, just with higher doses of the compounds (abortifacient, allergenic, narcotic, nephrotoxic, and hepatotoxic) Glycosides of triterpenes and saponins are water soluble and are stored in an inactive form in the vacuole. When the plant is attacked they are converted to an active form that exhibits membrane activity. Monodesmosidic saponins can complex cholesterol in biomembranes with lipophilic terpenoid moiety, and bind to glycoproteins and glycolipids with their sugar moiety. Creates tensions and leakage. Explains use in overcoming external infections. Internal use at low doses because of toxicity. Steroids, triterpenes and saponins structurally resemble endogenous hormones, e.g., glucocorticoids. Anti‐inflammatory effect is possible due to a corticomimetic effect. Cortisone Diosgenin Progesterone Cardiac glycosides are a special case of steroidal saponins that inhibit NA+/K+‐ATPase and are therefore strong toxins. They have a specific effect on the dynamics and rhythm of the heart. Pharmacologically the various structures have similar physiological effects. These are: Positively inotropic (inotropy: ability to contract) Negatively chronotropic (chronotropy: ability to initiate an electrical impulse) Negatively dromotropic (dromotropy: ability to conduct an electrical impulse) Positively bathmotropic (bathmotropy: ability to respond to direct mechanical stimulation) Differences relate to absorption rate, latency, duration of action and risk of accumulation (see later).