Synthesis, Molecular Docking Studies and Biological Evaluation of N-Acylarylhydrazones as Anti-Inflammatory Agents.

In the present work a series of N'-arylidene-2-(benzamido)-3-(naphthalen-2-yl)acrylohydrazides were synthesized by refluxing the intermediate 2-(benzamido)-3-(naphthalen-2-yl)acrylohydrazide with various substituted benzaldehyde in the presence of glacial acetic acid. The intermediate 2-(benzamido)-3-(naphthalen-2-yl)acrylohydrazide 2 was prepared by stirring 4-((naphthalen-2-yl)methylene)-2-phenyloxazol-5(4H)-one with hydrazine hydrate in the presence of absolute ethanol. The chemical structures of the compounds were established by IR, 1H NMR and mass spectral data. All the compounds were evaluated for anti-inflammatory (in vivo, in vitro) activity and performed docking against COX-2. The compounds 3a, 3c and 3o showed good inhibition of COX-2 in in vitro studies (0.75 µM, 0.5 µM and 0.7 µM as IC50, respectively). The compounds 3c, 3e and 3f were found to be more active than standard drug phenylbutazone at equidose. Molecular docking studies showed that compound 3 m exhibited good binding affinity against COX-2 with docking score 9.328 kcal/mol, when compared to the standard celecoxib.

Mutation Analysis of SARS-CoV-2 Variants Isolated from Symptomatic Cases from Andhra Pradesh, India.

There has been a continuous evolution in the SARS-CoV-2 genome; therefore, it is necessary to monitor the shifts in the SARS-CoV-2 variants. This study aimed to detect various SARS-CoV-2 variants circulating in the state of Andhra Pradesh, India. The study attempted to sequence the complete S-gene of SARS-CoV-2 of 104 clinical samples using Sanger's method to analyze and compare the mutations with the global prevalence. The method standardized in this study was able to amplify the complete length of the S-gene (3822 bp). The resulting nucleotide and amino acid mutations were analyzed and compared with the local and global SARS-CoV-2 databases using Nextclade and GISAID tools. The Delta variant was the most common variant reported in the present study, followed by the Omicron variant. A variant name was not assigned to thirteen samples using the Nextclade tool. There were sixty-nine types of amino acid substitutions reported (excluding private mutations) throughout the spike gene. The T95I mutation was observed predominantly in Delta variants (15/38), followed by Kappa (3/8) and Omicron (1/31). Nearly all Alpha and Omicron lineages had the N501Y substitution; Q493R was observed only in the Omicron lineage; and other mutations (L445, F486, and S494) were not observed in the present study. Most of these mutations found in the Omicron variant are located near the furin cleavage site, which may play a role in the virulence, pathogenicity, and transmission of the virus. Phylogenetic analysis showed that the 104 complete CDS of SARS-CoV-2 belonged to different phylogenetic clades like 20A, 20B, 20I (Alpha), 21A (Delta), 21B (Kappa), 21I (Delta), 21J (Delta), and 21L (Omicron).