Methoxy‐activated indole‐7‐carbohydrazides; synthesis, antioxidant, and anticancer properties

Abstract

Indole has been known as a key heterocyclic motif in the development of new structures for both chemical and biological properties. In this current study, a new range of indole-7-carbohydrazides has been successfully synthesized starting from the readily available 3-phenyl and 2,3-diphenyl 4,6-dimethoxyindoles.The structures of the novel compounds were confirmed by utilizing 1 H NMR, 13 C NMR, FT-IR, high-resolution mass spectrometry, and single crystal X-ray diffraction techniques. In addition, the indole-7-carbohydrazides showed promising antioxidant results in preliminary screens. Some of the new compounds generated from dimethoxy indoles were also screened for their anticancer activity against SH-SHY5Y (human neuroblastoma), AGS (human gastric adenocarcinoma), and MDA-MB-231 (human breast adenocarcinoma) cell lines. The results revealed that the compound 12 was the promising candidate, showing cytotoxic effects on both neuroblastoma, stomach, and breast cancer cells.

Synthesis of New Methoxy Actived Mono and Bis-indole Compounds

“…Therefore, the experiment was repeated by in a mixture of THF and methanol and it was determined that the starting material was exhausted after 24 hours. After the reaction, it was also determined that the indole-7-hydrazonomethyl 6 is highly reactive and has rapid degradation potential and therefore it was used for the next reaction shortly after its synthesis [35]. In the last step, compound 6 was spun in acetone at room temperature and the targeted indole 7 was successfully synthesized (figure 3).…”

The anti‐breast cancer potential of indole/isatin hybrids

“…Isatin‐carbohydrazide hybrids also possessed promising activity against BC cells, and among them, hybrid 77 (IC 50 : 0.99 µM) was fivefolds more potent than sunitinib (IC 50 : 4.77 µM). [ 118,119 ] Moreover, isatin‐thiosemicarbazone hybrid 78 (IC 50 : 23.42 and 19.68 µM) demonstrated potential activity against MCF‐7 and MDA‐MB‐231 cell lines. [ 120 ]…”

Insight into Indole‐Based Heterocyclic Scaffolds: A Medicinal Chemistry Perspective

“…Hakan Kandemir et al [118] reported a protocol for synthesis of 7-hydrazonomethyl-4,6-dimethoxyindoles 575 (a-b) and 4,6dimethoxyindole based carbohydrazides 576 (a-j). Initially 4,6dimethoxyindoles 573 (a-b) were reacted with POCl 3 and DMF at 0 °C for 6 h to yield indole-7-carbaldehydes 574 (a-b) followed by reaction with hydrazine and ethanol at room temperature yielded corresponding 7-hydrazonomethyl indoles 575 (a-b).…”

“…Hakan Kandemir et al [118] . reported a protocol for synthesis of 7‐hydrazonomethyl‐4,6‐dimethoxyindoles 575 (a–b) and 4,6‐dimethoxyindole based carbohydrazides 576 (a–j) .…”