Metal-Free, Visible-Light-Mediated Synthesis of Tetracyclic Benzimidazole: Regioselective C–H Functionalization with In Vitro and Computational Study of Anti-breast Cancer Compounds

ACS Omega, Journal Year: 2025, Volume and Issue: 10(6), P. 5778 - 5794

Published: Feb. 3, 2025

Globally, breast cancer is the leading cause of mortality. Within field antibreast drug design by several compound docking studies, eight new N-containing nonsteroid tetracyclic derivatives have been synthesized via regioselective intramolecular C-H functionalization visible light. The adopted methodology highly efficient, green, and sustainable to unload a pathway with excellent yield. It offers rapid, low-cost, catalyst-free method for creating physiologically active molecules from easily accessible substrates. substances were described using spectroscopic methods like HRMS, 1HNMR, 13CNMR, XRD analysis. This study explores cytotoxic potential novel compounds against human MCF-7 cells. includes in vitro experiments assess effect our on These include cytotoxicity assessment cell cycle, apoptosis, MTT test analysis flow cytometry, reactive oxygen species (ROS) production assessment, etc. Among compounds, 2e exhibited most potent activity, an inhibitory concentration (IC50) 40 nM, surpassing efficacy established drugs such as exemestane (IC50 24.97 micromolar) tamoxifen 5.45 μM). Compound also significantly induced apoptosis cycle arrest G1 phase, increasing apoptotic population 65.97%. Additionally, led marked rise level ROS generation, implicating oxidative stress its mechanism action. Molecular dynamic simulation further supported vigorous anticancer activity 2e, demonstrating promise effective treatment.

Language: Английский

Design, Synthesis, And Biological Evaluation of 1‐H Indazole Derivatives As Novel Target (CYP51) Antifungal Inhibitors

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(16)

Published: April 1, 2025

Abstract The rise in drug‐resistant fungal infections has intensified the need for novel antifungal agents, particularly those targeting cytochrome P450 51 (CYP51) a key enzyme ergosterol biosynthesis. This study explores design, synthesis, and biological evaluation of 1H‐indazole derivatives as potential CYP51 inhibitors. Structure‐based virtual screening identified seventeen indazole‐based candidates, which were further assessed pharmacokinetic properties including absorption, distribution, metabolism, excretion, toxicity (ADMET) using computational approaches. Two lead compounds, 1aa 2aa synthesized evaluated their activity against Rhizopus oryzae . Among them, compound exhibited superior efficacy with minimum inhibitory concentration (MIC) 128 µg/mL, while displayed an MIC 256 µg/mL. In vitro assays confirmed that effectively inhibited biosynthesis correlating its strong binding affinity to heme group CYP51, demonstrated by molecular docking dynamics simulations. These findings highlight promising optimization offering strategy combat resistance clinical settings.

Language: Английский