Synthesis of 1-(4-hydroxy-3-methoxyphenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid derivatives as mast cell stabilizers

Autor: Ramanpreet Shah, Jatinder Singh, Dhandeep Singh, Karan Singh Saini, Jaspreet Kaur, Dimple Sethi Chopra, Ram Sarup Singh, Amteshwar Singh Jaggi, Nirmal Singh
Rok vydání: 2020
Předmět:
Zdroj: Medicinal Chemistry Research. 29:1400-1412
ISSN: 1554-8120
1054-2523
DOI: 10.1007/s00044-020-02555-y
Popis: The role of mast cells can be protective or harmful; depending upon the physiological/pathological condition in which they get activated. The latter role is due to mast cell degranulation and release of an array of incendiary mediators. Mast cells have a well-established role in diseases like allergy, eczema, anaphylactic shock, mastocytosis, and other miscellaneous mast cell diseases. Previously, we have shown that spiro-β-carboline alkylated analogs have mast cells stabilization activity. Recently, tryptophan has been reported to suppress the mast cell activation. Indeed, vanillin analogs were reported to inhibit degranulation. Hence, it is worthwhile to synthesize 21 constrained analogs of tryptophan with vanillin which are derivatives of 2,3,4,9-tetrahydro-β-carboline-3-carboxylic acid and their evaluation for ex-vivo inhibition of the compound 48/80 induced mast degranulation activity. By comparing IC50 (µM) values with standard drug cromolyn sodium (IC50 = 0.486 ± 0.003 µM), the bulky group compounds like tri-substituted isopropyl (compound 7; cis-1-(4-Isopropoxy-3-methoxyphenyl)-2,9-diisopropyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid; IC50 = 0.389 ± 0.015 µM) and tri-substituted octyl (compound 17; cis-1-(3’-Methoxy-4’-(octyloxy)phenyl)-2,9-dioctyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid; IC50 = 0.237 ± 0.031 µM) were found to be equipotent. Furthermore, the polar group SO2 containing compound tosyl derivative (compound 21; cis-1-(4’-hydroxy-3’-methoxyphenyl)-2-tosyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid; IC50 = 1.16 ± 0.080 µM) also showed marked potency. This is an important study of β-carboline derivatives showing mast cell stabilization having a wider scope in mast cell research, although their mechanism remains to be unknown.
Databáze: OpenAIRE
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