Synthesis of 1,4-dihydropyrazolo[4,3-b]indoles via intramolecular C(sp2)-N bond formation involving nitrene insertion, DFT study and their anticancer assessment

A Minireview on the Scope of Cadogan Cyclization Reactions Leading to Diverse Azaheterocycles

“…We further tested all the synthesized compounds for their anticancer activity against various cancer cell lines such as A549, HCT-116, and MDA-MB-231 (breast cancer), and MCF-7. [43] Interestingly, all the compounds exhibited low IC 50 values in the μM range, however, compounds 80 a-c were found to exhibit potent antiproliferative activities against all the four cancer cell lines as compared to reference drugs i. e. camptothecin and doxorubicin. Later, to find the toxicity of these lead compounds 80 a-c on normal cells, human peripheral blood mononuclear cells (hPBMCs) were used and the results from the MTT assay showed no significant toxicity at 10 and 25 μM concentration of these compounds for 48 h. Furthermore, these compounds were tested for topoisomerase inhibitory activity, cell cycle arrest, ROS generation and alteration in mitochondrial membrane potential.…”

“…Therefore, the team provided the researchers with an opportunity to synthesize compounds with a wide variety of substitutions at N-1, C-3 and N-4 positions of the discussed indole-based scaffold, further leading to generate SAR for medicinal chemistry viewpoint. [43]…”

“…In 2021, our group synthesized a novel series of 1,4‐dihydropyrazolo[4,3‐ b ]indoles from various 5‐(2‐nitrophenyl)‐1 H ‐pyrazole [42] precursors through intramolecular C−N bond formation using Cadogan cyclization (Scheme 18), and performed a DFT study to support the involvement of nitrene insertion in the mechanism of the reaction. We further tested all the synthesized compounds for their anticancer activity against various cancer cell lines such as A549, HCT‐116, and MDA‐MB‐231 (breast cancer), and MCF‐7 [43] . Interestingly, all the compounds exhibited low IC 50 values in the μM range, however, compounds 80 a – c were found to exhibit potent antiproliferative activities against all the four cancer cell lines as compared to reference drugs i. e. camptothecin and doxorubicin.…”

“…Moreover, these compounds induced ROS generation, and altered the mitochondrial membrane potential of MDA‐MB‐231 cells. Therefore, the team provided the researchers with an opportunity to synthesize compounds with a wide variety of substitutions at N‐1, C‐3 and N‐4 positions of the discussed indole‐based scaffold, further leading to generate SAR for medicinal chemistry viewpoint [43] …”

29th Annual GP2A Medicinal Chemistry Conference

“…Nowadays, C-N bond formation has been increasingly used to construct diverse N-heterocycles with various applications in pharmaceuticals, supramolecular chemistry, and so on. We herein for the first time have reported a new synthetic route for 1,4dihydropyrazolo [4,3-b]indoles via deoxygenation of o-nitrophenyl-substituted N-phenyl pyrazoles, and subsequent intramolecular C(sp 2 )-N bond formation under modified microwave Cadogan condition [126]. This method exhibits a good substrate scope, and it allows access to NH-free as well as N-substituted fused indoles, which can present a potential utility in pharmaceutical as well as supramolecular chemistry applications.…”