We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

ABSTRACT A series of molecules bearing multiple functional groups were synthesized to study their antibiotic effect against Gram-positive and Gram-negative bacteria and lipoxygenase activity as well. 2,4-Dimethylcarbolic acid (1) was refluxed with ethyl 2-bromoacetate to synthesize ethyl 2-(2,4-dimethylphenoxy)acetate (2). Compound 2 was converted to the corresponding hydrazide 3, again on refluxing with hydrazine. The compound 5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-thiol (4) was synthesized by the reaction of 3 and CS2 in the presence of KOH. Compound 4 was further converted to the corresponding ester 5 and then 2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide (6). The final molecules N'-substituted-2-(5-((2,4-dimethylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)acetohydrazide, 8a-m, bearing ether, 1,3,4-oxadiazole, thioether, hydrazone and azomethine functional groups were synthesized by stirring the aryl carboxaldehydes 7a-m with 6 in methanol at room temperature. The depicted structures of all synthesized molecules were corroborated by IR, 1H-NMR and EIMS spectral data analysis. 8m and 8i showed substantial antibacterial activity and lipoxygenase inhibitory activity, respectively.

The synthesis of poly-functional moieties as one unit has been under consideration by the synthetic chemists to search out new potent molecules. 2-Chlorobenzoic acid (1) was converted to 5-(2-chlorophenyl)-1,3,4-Oxadiazol-2-thiol (4) through a series of steps. This nucleophile was attached with different electrophiles, prepared by the reaction of aryl/alkyl amines with 2-bromoacetylbromide, in NaH/DMF to synthesize N-substituted-2-((5-(2-chlorophenyl)-1,3,4-Oxadiazol-2-yl)sulfanyl)acetamide, 7a-f. The molecule 4 was stepped to ethyl ester and carbohydrazide. The carbohydrazide was made to react with aryl carboxaldehydes in methanol to synthesize N'-substituted-2-(5-(2-chlorophenyl)-1,3,4-Oxadiazol-2-ylthio)acetohydrazide, 11a-i. The structures of all the molecules were corroborated through IR, ¹H-NMR and EI-MS spectral data. Both the series were screened for antibacterial and enzyme inhibition activity.

We used ultraviolet (UV) radiation to induce mutation in three locally isolated strains of Escherichia coli. Different dilutions of bacterial cultures were exposed to UV lamp of 254 nm wavelength for different time intervals at varied distances ranging from 5 to 210 sec and 5 to 100 cm. Viable colonies were screened for mutants with an increased production of penicillin G acylase (PGA) and a reduced production of β-lactamase, which are the desired properties of PGA producing industrial strains. A survival curve was made to get optimum exposure time and distance. The survival percentage for each exposure period was calculated and 1-5% survival was found useful for obtaining mutants with desired change. Screening for PGA and β-lactamase constitutive and/or deficient mutants was made by Serratia marcescens overlay test. A total of 100 survivors were selected of which 49% expressed PGA activity higher than the parent strain. Frequency of β-lactamase constitutive and deficient mutants was 48 and 52%, respectively. The best hyper-producing mutant (BDCS-N-M74), with almost negligible expression of β-lactamase, exhibited three-fold (22.5 mg 6-APA h-1 mg-1 wet cells) increase in PGA activity compared with that in the parent strain (6.7 mg 6-APA h-1 mg-1 wet cells). The results indicated the successful induction of UV mediated mutation in E. coli for PGA hyper-producing mutants lacking β-lactamase activity.