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‐1H‐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 (IC₅₀∼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.

中文翻译：

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声化学合成6-取代的吲哚[3'，2'：4,5]吡咯并[2,3-b]喹喔啉衍生物作为潜在的细胞毒剂

在目前的研究中，我们已经探索吲哚并6-取代[3'，2'：4,5]吡咯并[2,3- b ]喹喔啉衍生物作为潜在的细胞毒性剂。这些化合物很容易通过2-氯-3-（2-氯-1 H-吲哚-3-基）喹喔啉与适当的胺在超声辐射下反应以良好的收率得到。使用基于细胞的测定法对所有这些化合物针对MDA-MB-231和MCF-7细胞系进行体外测试，然后使用基于酶的测定法针对SIRT1（或瑟土因1）进行体外测试。化合物3a [i。e。6-（4-甲氧基苄基）-6,7-二氢吲哚[3'，2'：4,5]吡咯并[2,3- b]喹喔啉]表明希望的（分别在10μM61和54％）二者的MDA-MB-231和MCF-7细胞系的生长抑制和SIRT1（IC的抑制₅₀ ~2.09±0.40μM体外）。此外，分子建模研究表明3a与几个残基e相互作用。G。SIRT1活性位点上的GLU345，ILE347，PHE273，ILE270，PHE312，PRO271，ILE279，ILE316估计总能量= -99.90 kcal / mol ，计算机模拟ADME认为3 a是潜在的命中分子。