Premium
Sonochemical Synthesis of 6‐Substituted Indolo[3′,2′:4,5]pyrrolo[2,3‐ b ]quinoxaline Derivatives as Potential Cytotoxic Agents
Author(s) -
Rao Mandava V. B.,
SriLaxmi Dandamudi,
Vardhini Suryadevara V.,
Guttikonda Venkata R.,
Kapavarapu Ravikumar,
Pal Manojit
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202002951
Subject(s) - quinoxaline , adme , chemistry , stereochemistry , in vitro , cytotoxic t cell , amine gas treating , lead compound , in silico , combinatorial chemistry , biochemistry , organic chemistry , gene
In the current study, we have explored 6‐substituted indolo[3′,2′:4,5]pyrrolo[2,3‐ b ]quinoxaline derivatives as potential cytotoxic agents. These compounds were readily prepared via the reaction of 2‐chloro‐3‐(2‐chloro‐1 H ‐indol‐3‐yl)quinoxaline with an appropriate amine under ultrasound irradiation in good to acceptable yields. The in vitro testing of all these compounds against MDA‐MB‐231 and MCF‐7 cell lines using a cell‐based assay and then against SIRT1 (or sirtuin 1) using an enzyme‐based assay was performed. The compound 3 a [i. e. 6‐(4‐methoxybenzyl)‐6,7‐dihydroindolo[3′,2′:4,5]pyrrolo[2,3‐ b ]quinoxaline] showed promising growth inhibition of both MDA‐MB‐231 and MCF‐7 cell lines (61 and 54 % at 10 μM, respectively) and inhibition of SIRT1 (IC 50 ∼2.09±0.40 μM in vitro). Moreover, molecular modelling studies indicated interaction of 3 a with several residues e. g. GLU345, ILE347, PHE273, ILE270, PHE312, PRO271, ILE279, ILE316 at the active site of SIRT1 with estimated total energy=−99.90 kcal/mol and the ADME prediction in silico suggested 3 a as a potential hit molecule.