Design, Synthesis and Molecular Docking Studies of Novel Thiadiazole Analogues with Potential Antimicrobial and Antiinflammatory Activities

Abstract

Background: Chemical modification of thiadiazole may lead to a potent therapeutic agent. In this study, biological properties of thiadiazole derivatives were evaluated by assessing their antimicrobial and anti-inflammatory activities. Methods: A series of novel derivatives of N-(5-(1-methyl-indol-3-yl)-1,3,4-thiadiazol-2- yl)-2-(5-substitutedphenyl)-3-(phenylamino)-4,5-dihydropyrazol-1-yl) acetamide have been synthesized and evaluated for their antimicrobial activity. Anti-inflammatory activity was done using carrageenan-induced inflammation in rat paw edema model. In-silico molecular docking studies of the synthesized compounds were performed on crystal structures of Aspergillus niger, Bacillus subtilis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Cyclooxygenase-2 (obtained from www.rcsb.org) using GRIP batch docking method of V-life MDS 3.0 software. The structures of the newly synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy. Results: Antimicrobial and Anti-inflammatory activity study of the novel synthesized compounds were screened. Synthesized compounds having methoxy substitution on the 3rd and 4th positions of aromatic ring are utmost active amongst all the derivatives. Compounds 6d, 6i, 6j and 6l were found to possess good anti-inflammatory activity having percentage of inhibition to the extent of 46.8%, 48.1%, 49.4%, and 48.5% as compared with Diclofenac. Conclusion: The experimental results were further supported by molecular docking analysis describing the better interaction patterns.

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

“…They used carrageenan-induced inflammation in rat paw oedema model to screen for the anti-inflammatory activities of the derivatives. Compounds 15a , 15b , 15c , and 15d ( Figure 2 ) were found to possess good anti-inflammatory activity having percentage of inhibition to the extent of 46.8%, 48.1%, 49.4%, and 48.5%, respectively, whereas the effects of the standard drug, diclofenac were 50.0% 30 .…”

Novel Quinolone substituted 1,3,4-oxadiazole derivatives: Design, synthesis, antimicrobial and anti-inflammatory potential

“…In this investigation, the docking score and H-bond interactions of synthesized derivatives were computed and shown as dotted green color lines. Out of all screened compounds, twelve derivatives were estimated to be having best binding a nity in terms of kcal/mol with common residues (ARG72, ARG78, ARG57, LYS32, SER49, LEU54, ILE94, ALA6, THR100, PHE31, MET16) and exhibited con rmed free energy of binding ranged from -4.5 to -8.6 kcal/mol, as shown in gures (2)(3)(4)(5)(6)(7)(8)(9)(10)(11). Compound 4f, 4h & 4k estimated best free energy of binding, -8.4, -8.6 & -8.5 kcal/mol into the binding pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands, as represented in gure 2, 5 & 8 and exhibited highest hydrogen bonding interaction with amino acids ARG57, ARG72 & ARG78.…”

“…[3]. Based on a literature review, quinolones demonstrated several biological pro les in addition to their ability to ght bacteria like anti-in ammatory [4][5], anti-HCV [6], anti-cancer [7][8][9][10][11], antimalarial [12][13], anti-HIV [14][15], and antidepressant activities [16]. Many quinolone derivatives are used in clinics as antibacterial drugs, such as MCB3837, MCB3681, CBR-2092 (rifamycin-quinolone conjugate), and Ro-23-9424 (in phase II clinical study) to treat a variety of infections [17][18][19].…”

Synthesis, Characterization, And Evaluation Of The Antibacterial Activity Of Novel 5-aryl-2-amino 1,3,4 Thiadiazole Derivatives

“…Many studies have seen that molecules with thiadiazole moiety in their structures exert many pharmacological activities. For example, antiinflammatory [6], anticancer [7,8], anticonvulsant [9], antituberculosis [10], and antidiabetic [11,12]. Furthermore, many pieces of researches supported that this group exhibits promising activity against a wide range of bacterial strains [13,14].…”