N‐hydroxy‐substituted 2‐aryl acetamide analogs: A novel class of HIV‐1 integrase inhibitors

Abstract

An in silico method has been used to discover N-hydroxy-substituted 2-aryl acetamide analogs as a new class of HIV-1 integrase inhibitors. Based on the molecular requirements of the binding pocket of catalytic active site, two molecules (compounds 2 and 4b) were designed as fragments. These were further synthesized and biologically evaluated. In vitro potency along with docking studies highlighted compound 4b as an active fragment which was further used to synthesize new leads as HIV-1 integrase inhibitors. Finally, six promising compounds (compounds 5b, 5c, 5e, 6-2c, 6-3b, and 6-5b) were identified by integrase inhibition assay (>50% inhibition). Based on in vitro anti-HIV-1 activity in a reporter gene-based cell assay system, compounds 5d, 6s, and 6k were found as novel HIV-1 integrase inhibitors due to its better selectivity index. Additionally, docking study revealed the importance of H-bond as well as hydrophobic interactions with Asn155, Lys156, and Lys159 which were required for their anti-HIV-1 activity.

Conformational Perturbation of SARS-CoV-2 Spike Protein Using N-Acetyl Cysteine, a Molecular Scissor: A Probable Strategy to Combat COVID-19

“…Å) as convergence criteria. 11 The protein coordinates of spike protein from the spike protein-ACE2 receptor (human) co-crystal (PDB code: 6LZG) was considered for investigating the binding mode of NAC. For docking study, the protein was prepared in SYBYL by making use of the same procedure as adopted in case of study molecule.…”

Studying of lipophilicity of potential biological active cyanoacetamide derivatives

“…Za izražavanje akutne toksičnosti se koristi koncentracija jedinjenja koja dovodi do imobilizacije 50% jedinki populacije izložene njegovom dejstvu tokom unapred definisanog vremenskog perioda (najčešće 48h) i označava se kao efektivna koncentracija, EC50 [17]. Imajući u vidu da amidi predstavljaju veliku i raznovrsnu grupu biološki aktivnih molekula sa širokom primenom u medicini [18][19][20][21][22][23], poljoprivredi [24][25][26] i biotehnologiji [27,28] u ovom radu je proučavano hromatografsko ponašanje i lipofilnost odabranih derivata cijanoacetamida, primenom tankoslojne hromatografije na obrnutim fazama u smeši vode i tri organska modifikatora ponaosob (tbutanola, N,N,-dimetilformamida (DMF) i dimetilsulfoksida (DMSO)). Primenom metode linearne regresije je ispitana zavisnost između dobijenih hromato-grafskih parametara (RM0 i m) i softverski iz-računatih vrednosti podeonog koeficijenta, log P, kao i odabranih farmakokinetičkih prediktora, odnosno parametara toksičnosti proučavanih derivata cijanoacetamida.…”