Introduction
Indole is a heterocyclic aromatic compound composed of a bicyclic structure. It consists of a six-membered benzene ring fused to a five-membered pyrrole ring, resulting in a unique and intriguing chemical structure. Found in various natural products such as serotonin, tryptophan, and auxins.
Reactivity: Reacts with electrophiles, nucleophiles, radicals, and metals to afford a wide range of substituted indole derivatives.
Functional Groups: Indole derivatives can have a wide range of functional groups, including halogens, amines, ketones, esters, and more.
Table 0
|
Properties |
|
|
Chemical Formula |
C8H7N |
|
Molecular Mass |
117.124 g/mol |
|
Appearance |
White Solid turn yellow on exposure to light. |
|
Melting Point |
52-54 degrees Celsius |
|
Acidity(pKa) |
16.2 |
|
Basicity(pKb) |
17.6 |
Indole Exhibits antimicrobial, anticancer, anti-inflammatory, and neuromodulator activities.
Anticancer Drugs
There are several U.S FDA has recently approved indole based anticancer agents such as
Vinblastine
Vinblastine sulfate 1, 2 has the molecular formula C46H58O9N4•H2SO4 and it is a dimeric alkaloid containing both indole and dihydroindole moieties.
IUPAC: Dimethyl(2β,3β,4β,5α,12β,19α)-15-[(5S,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-1,4,5,6,7,8,9,10-octahydro-2H-3,7-methanoazacycloundecino[5,4-b]indol-9-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidospermidine-3,4-dicarboxylate.
MOA: It binds to microtubular proteins in the mitotic spindle, thereby preventing cell division during metaphase. It also interferes with amino acid metabolism by inhibiting glutamic acid utilization and preventing purine synthesis, citric acid cycle, and urea formation.
Marketed Preparation
Panobinostat
Panobinostat 3, 4 sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). Panobinostat is used in combination with the anti-cancer drug bortezomib and the corticoid dexamethasone for the treatment of multiple myeloma in adults who had received at least two previous treatments, including bortezomib and an immunomodulatory agent.
Alectinib
IUPAC: 9-Ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H- benzo[b]carbazole-3-carbonitrile
Alectinib 5, 6 is indicated for the first-line treatment of adults with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC); 5 and for the treatment of adults with ALK‑positive advanced NSCLC previously treated with crizotinib.
Sunitinib
Sunitinib 7, 8 sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.
Osimertinib
Osimertinib 9, 10 is used to treat locally advanced or metastatic non-small-cell lung cancer (NSCLC), if the cancer cells are positive for the T790M mutation in the gene coding for EGFR or for activating EGFR mutations. The T790M mutation may be de novo or acquired following first-line treatment with other EGFR tyrosine kinase inhibitors, such as gefitinib, erlotinib, and afatinib.
NSAID
Indomethacin
IUPAC: 2-{1-[(4-Chlorophenyl) carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid
Indomethacin 13, 14 is a nonsteroidal anti-inflammatory drug (NSAID) used to treat mild to moderate acute pain and relieve symptoms of arthritis (osteoarthritis and rheumatoid arthritis) or gout, such as inflammation, swelling, stiffness, and joint pain.
MOA: Inhibits the synthesis of prostaglandins and prostaglandin synthesis.
Antiemetic
Ondansetron
IUPAC: (RS)-9-Methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3-dihydro-1H-carbazol-4(9H)-one
Ondansetron15, 16 is a selective antagonist of the 5-hydroxytryptamine3 (5-HT3) receptors and is a very effective agent in the prevention and treatment of nausea and vomiting. Ondansetron is used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery. It works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting
ED (Erectile Dysfunction Drugs)
Tadalafil
IUPAC: (6R,12aR)-6-(1,3-benzodioxol-5-yl)-2-methyl-2,3,6,7,12,12a-hexahydropyrazino [1',2':1,6] pyrido[3,4-b]indole-1,4-dione
MOA: Tadalafil 17, 18 is in a class of medications called phosphodiesterase (PDE) inhibitors. It works to treat erectile dysfunction by increasing blood flow to the penis during sexual stimulation.
Antimigraine agents
MOA: Triptans group drugs act as antimigraine agents by selectively binding to the serotonin receptors 5-HT1B and 5-HT1D
Marketed Preparation
Naratriptan 20
IUPAC: N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl] ethane-1-sulfonamide hydrochloride.
