Design, synthesis, biological evaluation and molecular docking studies of novel 3-substituted-5-[(indol-3-yl)methylene]-thiazolidine-2,4-dione derivatives

Various thiazolidine-2,4-dione derivatives 3a-l possessing indole moiety were designed, synthesized using appropriate conventional heating as well as microwave irradiation methods. All the synthesized compounds were characterized physically and spectrally. The compounds were evaluated for in vitro antibacterial activity, in vitro antioxidant activity and in vivo hypoglycemic activity in relation to the standard drugs. Most of the new compounds exhibited moderate activity and some showed considerable activity. Molecular docking studies were carried out using AutoDock software and revealed that compound 3b has significant binding interaction with PPARγ receptor compared with the standard ligand Rosiglitazone

Ultrasound assisted Mizoroki–Heck reaction catalyzed by Pd/C: Synthesis of 3-vinyl indoles as potential cytotoxic agents

AbstractThe Pd/C–PPh3 catalyst system facilitated the C–C bond forming reaction between 3-iodo-1-methyl-1H-indole and various terminal alkenes under ultrasound irradiation. The present ultrasound assisted Mizoroki–Heck coupling afforded a number of 3-vinyl indole derivatives in good to acceptable yields. Two of these indole derivatives showed cytotoxic activities against breast cancer cell lines

Ultrasound Assisted Cu-catalyzed Ullmann-Goldberg Type Coupling-cyclization in a Single Pot: Synthesis and inSsilico Evaluation of 11H-pyrido[2,1-b]quinazolin-11-ones Against SARS-CoV-2 RdRp

The in silico evaluation of 11H-pyrido[2,1-b]quinazolin-11-one derivatives against SARS-CoV-2 RdRp was undertaken based on the reports on antiviral activities of this class of compounds in addition to the promising interactions of the antiviral drug penciclovir as well as quinazoline derivatives with SARS-CoV-2 RdRp in silico. The target compounds were prepared via an Ullmann–Goldberg type coupling followed by the subsequent cyclization (involving amidation) in a single pot. The methodology involved a CuI-catalyzed reaction of 2-iodobenzoate ester with 2-aminopyridine or quinolin-2-amine or thiazol-2-amine under ultrasound to give the expected products in acceptable (51–93%) yields. The molecular interactions of the synthesized 11H-pyrido[2,1-b]quinazolin-11-one derivatives with the SARS-CoV-2 RdRp (PDB: 7AAP) were evaluated in silico. The study suggested that though none of these compounds showed interactions better than penciclovir but the compound 3a and 3n appeared to be comparable along with 3b seemed to be nearly comparable to favipiravir and remdesivir. The compound 3n with the best binding energy (-79.85 Kcal/mol) participated in the H-bond interactions through its OMe group with THR556 as well as ARG624 and via the N-5 atom with the residue SER682. The in silico studies further suggested that majority of the compounds interacted with the main cavity of active site pocket whereas 3h and 3o that showed relatively lower binding energies (-66.06 and -66.28 Kcal/mol) interacted with the shallow cavity underneath the active site of SARS CoV-2 RdRp. The study also revealed that a OMe group was favourable for interaction with respect to its position in the order C-8 \u3e C-1 \u3e C-2. Further, the presence of a fused quinoline ring was tolerated whereas a fused thiazole ring decreased the interaction significantly. The in silico predictions of pharmacokinetic properties of 3a, 3b and 3n indicated that besides the BBB (Blood Brain Barrier) penetration potential these molecules may show a good overall ADME. Overall, the regioisomers 3a, 3b and 3n have emerged as molecules of possible interest in the context of targeting COVID-19