Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling

Design and synthesis of novel series of 1,3,4-oxadiazoles containing FQs derivatives and screened their antibacterial, antimycobacterial properties. The synthesized compounds were characterized by different spectral techniques like IR, ¹H NMR, ¹³C NMR, mass and elemental analysis. The results of the antimicrobial activity and compounds 6d, 6b, 6e, 6f and 6a demonstrated potent antibacterial activities with zone of inhibition of 42, 36, 37, 34 and 30 mm against S. aureus, E. faecalis, S. pneumoniae, E. coli and K. pneumoniae, respectively. 1,3,4-Oxadiazole derivatives 6a, 6b, 6 g were showed excellent antimycobacterial activity against M. smegmatis H₃₇Rv with MICs 22.35, 16.20, 20.28 µg/mL, respectively. FQs 6d and 6b exhibited highest hydrogen bonding interactions with Asp83 (3.11 A?), Ser80 (2.15 A?) Asp27 (σ-σ), Arg87 (Π-Π), Arg87 (Π-Π), Ser80 (σ-σ), Ala84 (σ-σ) and binding energies ΔG?=????6.41, ??6.97 kcal/mol with active site of topoisomerase-IV from S. pneumoniae [4KPE]. We performed a computational investigation of compounds 6a–j for their absorption, distribution, metabolism and excretion (ADME) properties by using the Molinspiration, Molsoft toolkits. The ligands 6f, 6d and 6b reveal the highest pharmacokinetic properties and possess maximum drug-likeness model score 1.59, 1.46 and 1.23, respectively.

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Design and synthesis of oxaprozin-1,3,4-oxadiazole hybrids as potential anticancer and antibacterial agents

In the present study, we report design, synthesis and screening of new novel 5-substituted-2-mercapto-1,3,4-oxadiazole analogues appended to oxaprozin for their in vitro anticancer and antibacterial activity. The synthesised compounds were characterized using various spectroscopic techniques. Furthermore, the structure of 5b (2-(2-[4,5-diphenyloxazol-2-yl]ethyl)-5-(ethylthio)-1,3,4-oxadiazole) was unequivocally confirmed by X-ray analysis. Among the series 5c (2-(2-[4,5-diphenyloxazol-2-yl]ethyl)-5-(propylthio)-1,3,4-oxadiazole) showed most promising anticancer activity against A549 cancer cell line and all the reported analogues manifested satisfactory safety profiles against human normal cell line HEK293T. The products exhibited good antibacterial activity and among the tested 5j (2-(2-[4,5-diphenyloxazol-2-yl]ethyl)-5-([4-fluorobenzyl]thio)-1,3,4-oxadiazole) exhibited most potent.     

Indirect determination of perchlorate by atomic absorption spectrometry

A liquid-liquid extraction and determination of perchlorate by atomic absorption spectrometry is described. The method involves extraction of perchlorate with the Schiffs base complex [Co(BPTC)₂]⁺, where BPTC = 2-benzoyl pyridine thiosemicarbazone, in methyl isobutyl ketone in acidic medium and subsequent analysis of cobalt in flame AAS, hence indirectly for perchlorate. The extraction efficiency is 98%. The calibration graph was found to be linear for 1.0–11.4 g ClO ₄ ^– per ml of solvent, and the limit of detection is 30 ng ml^–1. The present method is free from interference of large number of foreign ions. The method has been applied for determination of perchlorate in human blood serum samples spiked with perchlorate, urine and commercial potassium chlorate sample.     

Nonsteroidal anti-inflammatory drugs based new 1,2,3-triazole derivatives: Their design,one-pot synthesis and in vitro evaluation

A series of novel and small molecules containing structural features of some well-known nonsteroidal anti-inflammatory drugs (NSAIDs) such as mefenamic acid or ibuprofen or naproxen and a heterocyclic moiety, for example, benzoxepine or quinoline were designed where a substituted 1,2,3-triazole was used as a linker. These molecules were initially designed as potential antibacterial agents. Synthesis of these compounds was carried out using a Cu-catalyzed azide-alkyne cycloaddition (CuAAC) as the key step to construct the central 1,2,3-triazole ring. The methodology involved regioselective and in situ azide formation from a dichloro derivative of heterocycle followed by click reaction with the appropriate alkyne containing the NSAID framework in the same pot. This one-pot sequential reaction afforded 24 target compounds in good yields. To assess their antibacterial properties, all the synthesized compounds were tested against both Gram-positive and Gram-negative species bacterial strains. One compound was found to be effective against the Gram-negative species P. aeruginosa. This compound also showed selective cytotoxicity against two cancer cell lines (COLO-205 and HOP-62) but no significant effect against noncancerous cell line (HEK293).     

Novel 1,2,3-triazolo phosphonate derivatives as potential antibacterial agents

We describe the synthesis, characterization, and in vitro antibacterial evaluation of a library of novel compounds based on 1,2,3-triazolo phosphonate framework along with the evaluation of DNA gyrase inhibitory potential of a promising molecule in silico. Preparation of these compounds was carried out via a multistep sequence comprising of the Abramov reaction followed by the Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) as the key steps. Various α-hydroxyphosphonate derivatives containing either a secondary or tertiary alcohol at the α position were prepared. When screened for their antibacterial activities in vitro using a Gram-positive (Staphylococcus aureus) and three Gram-negative (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) strains, majority of these derivatives exhibited reasonable to good effects with the analogue 5k being active against all the strains. The SAR analysis indicated that the activity was influenced by the position of the α-hydroxyphosphonate moiety as well as the substituent present on the benzene ring attached to the 1,2,3-triazole ring. Moreover, the compound 5k showed strong interactions with the DNA active site when docked into the DNA gyrase in silico. Thus, the 1,2,3-triazolo phosphonate derivative 5k appeared to be a novel and promising hit molecule that deserves further study as a potential antibacterial agent.