Bitter SAR and ident. and uses

SAR of Sodium Cromoglycate (Key Features)?

essential for its mast cell stabilizing activity:
1. Coplanarity of the two chromone nuclei.
2. A flexible dioxy alkyl link.
3. Carboxyl groups at the C-2 positions.

SAR of Parthenolide (Cytotoxic Groups)?

Two reactive groups are required for its cytotoxic activity: 1. An α-methylene-γ-lactone ring. 2. An epoxide group.

Mechanism of Parthenolide's Cytotoxicity?

Its reactive lactone and epoxide groups interact with nucleophiles,(thiol groups of cysteine in cellular proteins), leading to cell cycle arrest and apoptosis.

SAR of Artemisinin (Essential Feature)?

The endoperoxide bridge within its trioxolane structure

Mechanism of Artemisinin's Activity?

The endoperoxide bridge is cleaved by iron to generate highly reactive free radicals & ROS

Cucurbitacins SAR: Which features INCREASE cytotoxic activity?

1. An α,β-unsaturated double bond at C23-C24.
   2. A keto group at C-3.
   3. An acetyl group at C-25
   4. A double bond at C1-C2.

Cucurbitacins SAR: Which features DECREASE cytotoxic activity?

1. Reduction of the C-3 keto group.
   2. Introduction of a hydroxyl group at C-24. (loss of DB)

Why is Cucurbitacin E highly cytotoxic?

Because it possesses all the features that increase activity: a C1-C2 double bond, a C23-C24 double bond, a C-3 keto group, and a C-25 acetyl group.

Podophyllin SAR: What structural features are required for anticancer activity?

1. trans intact lactone ring

Podophyllin SAR: How do alkalis affect its activity?

Strong alkali destroys activity by opening the lactone ring.
mild alkali change trans-fused stereochemistry.

bruceolide SAR: What is required for ANTITUMOR activity?

1. A diosphenol group at C2–C3.
   2. An ester at C-15 with α,β-unsaturation.
   3. A lactone carbonyl at C-16.

Bruceine D and E SAR C-15?

The presence of the ester at C-15 confers antitumor activity. OH confers antimalarial

(+)-Discodermolide SAR: What is the role of the C-21 tail?

A hydrophobic polyketide tail at C-21 is necessary for its anticancer activity.

(+)-Discodermolide SAR: What is the role of the carbamate group?

The carbamate group is required for activity, although it may be substituted.

(+)-Discodermolide SAR: What is the role of the lactone carbonyl?

The carbonyl group of the lactone ring is required to function as a hydrogen bond acceptor.

(+)-Discodermolide SAR: How important is its stereochemistry?

The specific stereochemistry and substitution pattern of the multiple hydroxyl (-OH) groups are essential for activity.

Khellin Identification Test 1 (Permanganate)?

decolorizes Potassium permanganate (KMnO₄) solution.

Khellin Identification Test 2 (Alkali)?

rose-red color with KOH or NaOH

How to distinguish Imperatorin from Xanthotoxin?

Reagents: Imperatorin reduces Ammoniacal silver nitrate or Fehling's solution
but no ppt with Wagner’s

Rotenone Identification Test?

Nitric acid (HNO₃),
then dil (NaOH) are added to an
acetone solution of rotenone.
blue color

Cantharidin Identification Test (insect source)?

Formaldehyde in dilute sulfuric acid.
A brown to black color

α-Santonin Identification Test 1 (Ferric Chloride)?

Reagents: Sulfuric acid (H₂SO₄) and ferric chloride (FeCl₃).
Result: A violet color is produced.

α-Santonin Identification Test 2 (Ethanolic Alkali)?

Reagents: Ethanolic KOH or NaOH.
Result: A violet-red color changes to reddish-yellow.

Picrotoxin Identification Test?

green with vanillin

Quassin Identification Test 1 (Sucrose)?

Reagents: Concentrated sulfuric acid (H₂SO₄) and sucrose.
Result: A red color is produced.

Quassin Identification Test 2 (Phloroglucin Test)?

crimson red with phloroglucinol and HCL

Brusatol/Bruceantin Derivatives Identification Test?

Reagent: Ferric Chloride (FeCl₃) solution. Result: A greyish-black because of diosphenol group.

Khellin & Visnagin (Vascular Uses)?

coronary and broncho-vasodilators to treat angina pectoris and chronic bronchial asthma.

Khellin (Phototherapeutic Use)?

Applied topically with UV light to treat skin conditions like psoriasis and vitiligo.
less SE than psoralens

Ammi visnaga Extracts (Renal Use)?

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.

Sodium Cromoglycate (Asthma/Allergy Use)?

Used as a first-choice agent for chronic asthma (inhaler), allergic conjunctivitis (eye drops), and orally for urticaria and food allergies.

Amiodarone Use?

Used as a coronary vasodilator to treat angina and antiarrhythmic agent

Psoralens Use?

vitiligo (skin depigmentation) and psoriasis, with UVA light (PUVA therapy).

Bergamottin Use?

antimutagenic & anticarcinogenic agent; inhibits CYP3A4, more toxicities.

Rotenone (Primary Use)?

insecticide.

Cantharidin (Topical Use)?

Used topically as a rubefacient (to cause skin redness) and a counter-irritant.

Deoxypodophyllotoxin Use?

hepatoprotective action; the leaves are used for jaundice.

Humulone (Uses)?

topical bacteriostatic

Lupulone (Use)?

sedative

Hops Extract (Commercial Use)?

Commonly used as an Over-the-Counter (OTC) sedative.

Cynarin Use?

Used for liver protection and as a choleretic (increases bile secretion), particularly in cases of jaundice.

Gossypol main Use?

Potential as a male contraceptive and for the treatment of uterine fibroids and endometriosis.

Gossypol (Antimicrobial/Antiparasitic Uses)?

Has demonstrated antiviral (against HIV, H5N1), antibacterial, and antiparasitic activity.

Gossypol (Anticancer Use)?

Shows promise as an anticancer agent for leukemia, lymphoma, and various carcinomas.

α-Santonin (Former Use)?

Formerly used as an anthelmintic for the treatment of roundworms (Ascaris), but now replaced due to toxicity.

Picrotoxin Use?

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

Parthenolide (feverfew plant)

Used for the treatment of migraine, headache, fever, and arthritis due to its anti-inflammatory properties.

Artemisinin (Primary Use)?

Used with its derivatives to treat drug-resistant Plasmodium falciparum malaria.

Artemisinin (Anticancer Uses)?

anti-angiogenic effect

Artemether (Specific Use)?

As a lipid-soluble derivative that can cross the blood-brain barrier, it is a first-line drug for cerebral malaria.

Columbin (Use)?

Used as a bitter tonic. (appetite stim.) (better than tannin as no iron ppt)

Quassin (Uses)?

Used as an insecticide and as an anthelmintic (administered as an enema) for the treatment of threadworms

What is Gossypol's unique isomerism?

It exhibits atropisomerism (restricted rotation around a single bond), causing it to exist as an enantiomeric mixture.

What is Chromo Santonin (Photo Santonin)?

A yellow isomeric form of α-Santonin that forms upon exposure to air and light. It can be regenerated back to santonin using ethanol.

What is the composition of Picrotoxin?

1:1 molecular mixture of two components: picrotoxinin and picrotin.

What is the chemical nature of Artesunate?

It is a semi-synthetic, water-soluble succinic acid derivative of artemisinin.

What is the chemical nature of Artemether?

lipid-soluble derivative of artemisinin for cerebral malaria

What is an alternate name for Xanthotoxin?

methoxalen.

What is an alternate name for Picrotoxin?

It is also known as Cocculin.

What are the side effects of Khellin?

It can induce elevated liver enzyme levels (like psoralens) and cause photosensitivity.

What is the full toxicity profile of α-Santonin?

Beyond vision effects ("xanthopsia"), large doses can cause epileptic convulsions and respiratory failure.

What are the contraindications for PUVA therapy?

It is contraindicated in pregnancy and for any patient with a history of skin cancer.

How is Silymarin's poor bioavailability improved?

Through formulations like Silipide (Siliphos), a
complex with lecithin that is 10 times more bioavailable.

How is Parthenolide's poor bioavailability being addressed?

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

In what forms are Ammi visnaga extracts used?

tea or in pills