bitter principles

What are bitter principles?

A diverse group of bitter-tasting compounds from various chemical groups, distinct from alkaloids and glycosides.

In which plant families are bitter principles commonly found?

They are abundant in families like Compositae, Labiatae, Gentianaceae, and Umbelliferae.

What are the two main classifications of bitter principles?

I. Non-Terpenoids and II. Terpenoids (Isoprenoids).

What are the subclasses of non-terpenoid bitters?

They are classified into six groups: 1. Chromone bitters, 2. Coumarin bitters, 3. Rotenoids, 4. Anhydride bitters, 5. Lignans and flavonolignans, and 6. Miscellaneous bitters.

What are the source and examples of furanochromone bitters?

Source: Fruits of Ammi visnaga. Examples: Khellin and visnagin.

What is the primary use of khellin and visnagin?

They are potent coronary and broncho-vasodilators used to treat angina pectoris and chronic bronchial asthma.

How is khellin identified in a lab test?

It decolorizes potassium permanganate solution and produces a rose-red color with KOH or NaOH.

What are the side effects of khellin?

It can cause elevated liver enzymes and photosensitivity.

How is khellin used in phototherapy?

Applied topically with UV light, it treats psoriasis and vitiligo with lower phototoxicity than psoralens.

How are Ammi visnaga extracts used?

As a tea or in pills to relieve renal colic, due to diuretic effects, smooth muscle relaxation, and inhibition of calcium oxalate stone formation.

What is sodium cromoglycate (Cromolyn) and how is it used?

A synthetic khellin analogue used for chronic asthma (nasal spray/inhaler), allergic conjunctivitis (eye drops), and orally for urticaria.

What is the mechanism of action for sodium cromoglycate?

It acts as a mast cell stabilizer, preventing the release of inflammatory chemicals like histamine. It has no muscle relaxant effect.

What structural features are essential for Sodium Cromoglycate's activity?

1. Coplanarity of the two chromone nuclei. 2. A flexible dioxy alkyl link. 3. Carboxyl groups at the C-2 positions.

What is amiodarone?

A synthetic khellin analogue used as a coronary vasodilator (for angina) and a potent antiarrhythmic agent.

What are examples of linear furanocoumarins (psoralens)?

Xanthotoxin, imperatorin, and bergapten.

What are the therapeutic uses of psoralens?

They are used to treat vitiligo and psoriasis, topically for small lesions and orally for multiple lesions.

What is PUVA therapy and what are its risks?

PUVA (Psoralen + UVA light) therapy can cause phototoxic reactions and increases the risk of squamous cell carcinoma. It is contraindicated in pregnancy or for patients with a history of skin cancer.

How can xanthotoxin be distinguished from imperatorin?

Imperatorin reduces ammoniacal silver nitrate and Fehling's solution, while Xanthotoxin does not. Both give a precipitate with Wagner's reagent.

What is the "grapefruit juice effect"?

Bergamottin and dihydroxybergamottin in grapefruit juice inhibit cytochrome P450 enzymes, preventing drug metabolism. This leads to elevated drug concentrations and increased risk of side effects.

What is the anticancer potential of furanocoumarins like bergamottin?

They show promise as antimutagenic and anticarcinogenic agents by inducing apoptosis and cell cycle arrest at the G2/M phase.

What are the source and primary use of rotenone?

Source: Roots of Derris and Lonchocarpus. Use: Primarily as an insecticide.

How is rotenone identified?

A solution in acetone, when treated with nitric acid and then dilute NaOH, produces a distinct blue color.

What are the source and use of cantharidin?

Source: The dried insect Cantharis vesicatoria (Spanish fly). Use: As a topical rubefacient (causes redness) and counter-irritant.

How are lignans biosynthesized?

They are derived from the dimerization of two C6-C3 (hemilignan) units, linked via a specific β-β coupling of the side chains.

What are the source and use of deoxypodophyllotoxin?

Source: Tujopsis dolabrata. Use: The pure compound has hepatoprotective (liver-protecting) action and its leaves are used to treat jaundice.

What is silymarin?

A standardized mixture of flavonolignans (silybin, etc.) from the fruits of Milk Thistle (Silybum marianum).

How is the poor bioavailability of silymarin improved?

Through formulations like Silipide (a complex with lecithin, 10x more bioavailable) or by creating glycosides of silybin.

What are humulone and lupulone?

Compounds from hops extract. Humulone has bacteriostatic action, and lupulone has sedative activity.

What is cynarin?

1,3-dicaffeoylquinic acid from artichoke leaves, used for liver protection and to increase bile secretion (choleretic).

What is gossypol and what is its key chemical property?

A phenolic, dimeric sesquiterpene from cotton seed that exists as an enantiomeric mixture due to atropisomerism (restricted rotation).

What is the specific link between gossypol and male infertility?

A correlation was found between low male fertility and the use of crude cotton seed oil for cooking. The oil must be refined to remove gossypol.

What is the primary toxicity of gossypol?

It impairs male and female reproduction. It also causes hemolytic anemia and impairs immune function.

What are the potential therapeutic uses of gossypol?

Potential as a male contraceptive, for treating uterine fibroids, and as an antiviral/antibacterial/antiparasitic agent.

What is the anticancer mechanism of gossypol?

It inhibits enzymes in energy production and DNA synthesis (like DNA polymerase and topoisomerase II), blocking the cell cycle at the G1/S checkpoint.

How are terpenoid bitters biosynthesized?

They are synthesized from isoprene units via the mevalonate pathway.

How are terpenoids classified?

By the number of isoprene units: Monoterpenoids (2), Sesquiterpenoids (3), Diterpenoids (4), Triterpenoids (6), and Tetraterpenoids (8).

What are sesquiterpene lactones?

C₁₅ lactone derivatives made from three isoprene units, classified by their carbocyclic skeletons (e.g., germacranolides, guaianolides).

What were the source and use of α-santonin?

Source: Dried flower heads of Artemisia maritima. Use: Formerly an anthelmintic for roundworms, but now replaced due to toxicity.

What is the characteristic toxicity of α-santonin?

It affects vision, causing "xanthopsia" (white objects appear green, blue, or yellow). Large doses can cause convulsions.

What is chromo santonin?

The yellow isomeric form of santonin produced when exposed to air and light. Santonin can be regenerated from it using ethanol.

How is α-santonin identified?

It gives a violet color with sulfuric acid and ferric chloride, and a violet-red color when warmed with alcoholic KOH or NaOH.

What is picrotoxin?

A 1:1 mixture of picrotoxinin and picrotin from the seed of Anamirta cocculus.

How are the components of picrotoxin separated and identified?

Separation: The two components are resolved by heating in benzene or chloroform; picrotoxinin dissolves while picrotin is insoluble. Identification: Picrotoxin gives a green color when heated with vanillin-HCl.

What is picrotoxin used for?

As a CNS and respiratory stimulant (analeptic), and as an antidote for barbiturate poisoning.

What are the source and use of parthenolide?

Source: The plant feverfew. Use: For migraine, headache, fever, and arthritis due to its anti-inflammatory properties.

What is the cytotoxic mechanism of parthenolide?

Its α-methylene-γ-lactone ring and epoxide group react with nucleophiles (like cysteine), causing G2/M-phase arrest and apoptosis in cancer cells.

How is the poor bioavailability of parthenolide being addressed?

By creating semisynthetic amino prodrugs, which have higher aqueous solubility and better pharmacokinetic profiles.

What is the source and key structural feature of artemisinin?

Source: Artemisia annua. It contains a unique endoperoxide bridge essential for its activity.

What is the primary use of artemisinin?

Used with its semi-synthetic derivatives to treat Plasmodium falciparum malaria. Monotherapy is discouraged due to resistance.

What is the mechanism of action for artemisinin?

It is a prodrug activated by iron. The endoperoxide bridge cleaves to form reactive free radicals that cause cell death, effective against both malaria parasites and cancer cells.

What are the specific anticancer advantages of artemisinin?

1. It is not transported by P-glycoprotein, thus avoiding multidrug resistance. 2. It can be combined with transferrin to specifically target leukemia cells.

What is artesunate?

A water-soluble, semi-synthetic derivative of artemisinin used for oral, rectal, IM, or IV administration.

What is artemether and why is it significant?

A lipid-soluble, semi-synthetic derivative of artemisinin that can cross the blood-brain barrier, making it a first-line drug for cerebral malaria.

What are the source and use of columbin?

A diterpene from the roots of calumba (Jateorhiza palmate). It is used as a bitter tonic and can be prescribed with iron salts because it contains no tannin.

What are the source and use of quassin?

A triterpene from Quassia amara. It is used as an insecticide and as an anthelmintic (enema for threadworms).

How is quassin identified?

It gives a red color with concentrated H₂SO₄ and sucrose, or a crimson red color with alcoholic phloroglucin and concentrated HCl