Synthesis of 2-Aryl Indazole: Synthesis, Biological Evaluationand In-Silico Studies.

In this work, a highly effective synthesis technique for obtaining aryl indazole under mild circumstances is provided, using trimethyl phosphine as a powerful reagent. The procedure shows that a wide range of substrates can be investigated, yielding various 2-aryl indazole derivatives with acceptable to exceptional yields and a wide range of functional group tolerance. Additionally, based on In Silico studies tests were conducted to determine the anticancer activity In Vitro for all produced compounds (3 a-3 j) against A549, HT-29 and HepG2 cell lines. Compounds 3 c and 3 d, with IC50 values of 15, 53.55, 7.34, 7.10, 56.28, and 17.87 (µM) against A549, HT-29 and HepG2 respectively, showed significant anticancer activity.

New Fluoroquinolone-1,2,4-triazoles as Potent Antibacterial Agents: Design, Synthesis, Docking Studies and in Silico ADME Profiles.

Our current work is aimed at synthesizing novel substituted 1,2,4-triazolyl-fluoroquinolone analogs and study of their biological activity to find active promising molecules. The structural elucidation of the products was demonstrated by a variety of spectroscopic methods such as IR, 1 H-NMR, 13 C-NMR, mass and elemental analysis. The newly synthesized 1,2,4-triazole derivatives were tested in vitro for their ability to inhibit the growth of seven different microbes including S. epidermidis, S. pneumoniae, S. aureus, B. subtilis, K. pneumoniae, E. coli, and P. aeruginosa. Five FQ derivatives 5d, 5e, 5h, 5j, and 5b have demonstrated good antibacterial activity against S. pneumoniae with MICs ranging from 2.5-22.0 µg/mL, while 5c, 5g reported comparable activity against P. aeruginosa with respect to the standard drugs moxifloxacin and ciprofloxacin. The possible mechanism of antibacterial activity of fluoroquinolones was investigated via molecular docking by using DNA gyrase of S. pneumoniae (3RAE). The pefloxacin derivatives also tended a good antibacterial ability based on the results of the molecular docking, ligand 5h with good binding affinity (-9.92 Kcal/mol) and binding site interactions via ValA:86, SerA:79, TyrA:82, MetA:116, AspA:78, AlaA:63, ArgA:117, ProA:112, ProA:113, AlaA:115, AlaA:114. These scaffolds were further evaluated for their ADMET and physicochemical properties by using SwissADME, ADMETlab2.0 web server as a good oral bioavailability.