Diclofenac‐Based Hydrazones and Spirothiazolidinones: Synthesis, Characterization, and Antimicrobial Properties

Abstract

We report here the synthesis, structural characterization, and biological evaluation of novel diclofenac-based hydrazone (4a-f) and spirothiazolidinone (5a-f, 6a-f) derivatives designed as potential antimicrobial agents. The compounds were evaluated in vitro for their antiviral activity against a wide spectrum of DNA and RNA viruses. They were further screened in vitro against different strains of bacteria and fungi. The hydrazone derivatives, 4a and 4c-f, were found to be active against herpesviruses (HSV-1, HSV-2, and HSV-1 TK ), vaccinia virus, and Coxsackie B4 virus, with EC values between 6.6 µg/mL and 14.7 μg/mL, and the selectivity index values were greater than 10 for 4a and 4f. The newly synthesized compounds (4-6) were inactive against the bacterial and the fungal strains tested, at levels below 2500, 1250, or 625 μg/mL. Interestingly, the key intermediate 3 with a free hydrazide moiety displayed antifungal properties against Candida albicans and C. parapsilosis at MIC values of 4.88 µg/mL and 78.12 μg/mL, respectively.

A new approach for the synthesis of N,N’-bis(phenoxyacetyl)hydrazines

“…There are several methods for the synthesis of 4-thiazolidinone derivatives and their mechanism of cyclization have been re-ported previously (Singh et al 1981, Hamama et al 2008Tripathi et al 2014, Kocabalkanlı et al 2017. One of the most common methods for obtaining 4-thiazolidinone ring is refluxing equimolecular amounts of aldimines or ketimines with alkanoic acids in dried aprotic solvents.…”

A review on advances in synthetic methodology and biological profile of spirothiazolidin‐4‐ones

“…Cihan-Üstünda g and group [81] communicated the preparation of spirothiazolidinone derivative 222 and its methyl analog bearing diclofenac residue. The acetohydrazides 220 on reaction with suitable ketone 44 and mercaptoacetic acid 3 in suitable solvents yielded corresponding spirothiazolidinones 222 (Scheme 50).…”

Design, synthesis, antitubercular and antiviral properties of new spirocyclic indole derivatives

“…Assignment of the indole protons was achieved on the basis of the values and coupling constants reported for the 2,3,5-trisubstituted indole ring [15,16,24,25]. The carbon resonances were assigned by chemical shifts and comparison with previously reported 13 C NMR data for compounds having a similar backbone structure [15,19,26]. CH 3 , CH 2 , CH, and C signals were assigned by…”