Synthesis, antimicrobial activity, and in silico studies of fluoroquinolones bearing 1,3,4‐oxadiazolyl‐triazole derivatives

Abstract

Compounds containing fluoroquinolone (FQ) moiety occupy privileged chemical space for discovering novel bioactive substances. In continuation of our research work, a new series of FQs linked to triazolyl–thiadiazine hybrids (3a–f) and triazolyl–oxadiazoles (5a–f) were developed as a new antimicrobial agent targeting DNA gyrase of Staphylococcus aureus. All the novel compounds have been characterized with IR, 1H NMR, 13C NMR, mass spectral analysis and elemental analysis. All the synthesized derivatives were investigated for their antibacterial effect against various bacterial and fungal strains. Against Gram‐positive bacteria S. aureus, compounds 3e, 5a, and 5d showed the highest antibacterial activity with minimum inhibitory concentrations (MIC) values 5.0 ± 0.04, 8.6 ± 0.03, and 6.1 ± 0.02 μg/mL, respectively. FQ derivatives 3a, 5c had the most potent antibacterial activity against Klebsiella pneumonia bacteria with MICs 6.4 ± 0.01, 4.1 ± 0.01 μg/mL and compounds 3e, 5d are active against Gram‐negative bacteria Bacillus cereus with MICs 8.3 ± 0.02, 10.0 ± 0.02 μg/mL, respectively. Interestingly, the molecules 3e were slightly more selective towards antifungal activity against Fusarium oxysporum (MIC 4.2 ± 0.01 μg/mL), compared to fluconazole (MIC 3.5 ± 0.01 μg/mL). In addition, a fascinating molecular modeling investigation showed that our FQs 3, 5 demonstrated good binding inhibition of S. aureus complex in DNS gyrase (2XCT) towards advancing an efficient medication against antibacterial disease. The prepared ligand 3c forms three hydrogen bonds with amino acid residues LysB:1043 (N23…NZ), ArgB:1092 (O20…NH), GlyB:1082 (O…N) with bond lengths 3.13, 2.15, 2.76 A°, respectively.

Synthesis of Benzimidazole Based 1,2,4‐Triazole Derivatives as Potential Anticancer Agents: In Silico Techniques

“…The 1,2,4‐triazole core has been brought into a great many restoratively intriguing particles to change them into better medications [18] . The 1,2,4‐triazole derivatives were begin with various biological activities such as antibacterial, [20] antifungal, [21] anticancer, [19] antileishmanial, [22] antihistaminic, [23] antidepressant, antitubercular, [24] anti‐inflammatory, [25] and analgesic [26] profiles. Based on the foregoing information, and in continuation of our past endeavors in the field of planning and combining novel bioactive heterocyclic compounds, this study focuses on the design and synthesis of a new arrangement of benzimidazole linked 1,2,4triazole derivatives that target the wild type of protein tyrosine phosphatase mutated in colorectal cancer (1WCH) [27] .…”

Design, Synthesis, in Vitro, and in Silico Evaluations of 1,3,4‐Oxadiazole Derivatives Linked to the Pyrrolo[2,3‐d]pyrimidine Moieties as Potent Antimicrobial Targets

“…Later, is a crucial structural component of many commonly used chemotherapeutic drugs, including the HIV medication Raltegravir, the antibacterial medicine furamizole, the anticancer drug zibotentan, the herbicidal and fungicidal agent oxadiazon, and the broad range antibacterial antibiotic furamizole (Figure 1). [8–11] The effectiveness of anticancer chemotherapeutic thymidylate synthase, [12] vascular endothelial growth factor receptors (VEGF), [13] epidermal growth factor receptors (EGFR), [14] focal‐adhesion kinase (FAK), [15] histone deacetylases (HDAC), [16] tubulin polymerase, [17] nuclear factor kB, [18] methionine aminopeptidase (MetAP), [19] and telomerase are the targets of 1,3,4‐oxadiazoles [20] . It has been noted that thymidine phosphorylase, an essential component of angiogenesis, is over expressed in a number of solid tumours [21] .…”