Assembly of Fully Substituted 2H‐Indazoles Catalyzed by Cu₂O Rhombic Dodecahedra and Evaluation of Anticancer Activity

Abstract

Simultaneous C−N, and N−N bond‐forming methods for one‐pot transformations are highly challenging in synthetic organic chemistry. In this study, the Cu2O rhombic dodecahedra‐catalyzed synthesis of 2H‐indazoles is demonstrated with good to excellent yields from readily available chemicals. This one‐pot procedure involves Cu2O nanoparticle‐catalyzed consecutive C−N, and N−N bond formation followed by cyclization to yield 2H‐indazoles with broad substrate scope and high functional group tolerance. Various cell‐based bioassay studies demonstrated that 2H‐indazoles inhibit the growth of cancer cells, typically through induction of apoptosis in a dose‐dependent manner. Moreover, 2H‐indazoles tested in the MDA‐MB‐468 cell line were capable of inhibiting cancer cell migration and invasion. Thus, it is shown that 2H‐indazoles have potent in vitro anticancer activity that warrant further investigation of this compound class.

Investigation on Photophysical, Solvatochromism and Biological Significance of Substituted 2H‐Indazole Derivatives

“…The synthetic methodology was initiated by the Cu 2 O rhombic dodecahedra catalyzed cyclization reaction between substituted 2-bromo-benzaldehyde 1, NaN 3 and aromatic amine 2 and 1,10phenanthroline as ligand in DMSO solvent to obtain substituted 2H-indazole 3 derivatives as shown in Scheme 2. [18] Once the reaction was successfully accomplished, the respective substituted 2H-indazole derivatives 3 were obtained by a simple work-up which involves the removal of catalyst and solvents under reduced pressure. Further steps involved extraction, and solvent evaporation.…”

“…The intermediate B then underwent electron reorganization followed by the removal of N 2 molecule and regeneration of Cu(I) catalyst to form the 2H-indazole derivative 3. [18]…”

“…[16] Several reports on the anticancer activity of fused heterocyclic compounds with IC 50 values are available in the literature. [17,18] Adding to this, these heterocyclics possess high target specificity, without displaying any cytotoxicity towards normal cells.…”

“…They also possess a wide spectrum of biological activities like antibacterial, antitumor, antifungal, antioxidant, antiviral, antimalarial and anthelmintic . Several reports on the anticancer activity of fused heterocyclic compounds with IC 50 values are available in the literature . Adding to this, these heterocyclics possess high target specificity, without displaying any cytotoxicity towards normal cells.…”

Computationally approached inhibition potential of Tinospora Cordifolia towards COVID-19 targets

“…Employing density functional theory [35] the geometry of all the molecules proposed as COVID-19 drug candidates, were optimized to understand structural features and hence their contribution to the inhibition or druggable potential. In continuation of our efforts to explore the potential application of synthesized bioactive compounds in our laboratory [36][37][38][39], for the first time, herein we are reporting the inhibitory effects of selected constituents of Tinospora Cordifolia on human ACE2 protein and the main protease of SARS-CoV-2 using molecular docking and pharmacokinetic studies. In this manuscript, we have investigated the various constituents of Tinospora Cordifolia for their potency to inhibit the host receptor for SARS-CoV-2 by molecular docking interactions.…”