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This paper presents the synthesis of some unique bi-heterocyclic hybrid molecules with a thiazole and an oxadiazole ring. The synthesis was initiated by the conversion of ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (1) to the corresponding 2-(2-amino-1,3-thiazol-4-yl)acetohydrazide (2) by the reaction with hydrazine hydrate in methanol. The treatment of the acid hydrazide, 2, with carbon disulfide gave the bi-heterocyclic nucleophile, 5-[(2-amino-1,3- -thiazol-4-yl)methyl]-1,3,4-oxadiazole-2-thiol (3). Finally, the target compounds, 5a–o, were synthesized by stirring the nucleophile 3 with different electrophiles, 4a–o, in DMF using LiH as a base and an activator. The structures of the newly synthesized molecules were confirmed through spectroscopic techniques, such as IR, EI-MS, 1H-NMR and 13C-NMR. The structure– –activity relationship of all these bi-heterocycles was established by evaluating them against four enzymes, namely, acetylcholinesterase, butyrylcholinesterase, urease and -glucosidase, followed by their in silico study. Moreover, their cytotoxicity was also profiled by killing data of brine shrimps at various concentrations.

The study describes the development and preliminary validation of a simple reverse-phase chromatographic method for determination of a novel drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM), in bulk and stressed solution, in order to find out the intrinsic stability behavior of the compound. Isocratic elution was carried out at a flow rate of 1.0 mL min-1 through a Promosil C18 column maintained at 25 °C, using the mobile phase comprising acetonitrile and aqueous o-H3PO4 (pH 2.67) (1:1, V/V). Detection was performed at 258 nm. The response of the detector was linear in a concentration range of 1.25-50.00 μg mL-1 with the correlation coefficient of 0.9996 ± 0.0001. Cumulative intra-day, inter-day and inter-instrument accuracy (99.5 ± 1.0, 100.2 ± 1.0 and 100.3 ± 0.4 %, resp.) with RSD less than 5 % indicated that the method was accurate and precise. The resolution and selectivity factor (>2 and >1, resp.), particularly in copper metal- and dry-heat-stress solutions, depicted the selectivity of the method. OXCPM remained stable under hydrolytic (acidic and neutral pH, ≤ 37 °C), photolytic and moist heat stress conditions. Under alkaline conditions (hydrolytic and photolytic), polar products were formed that eluted very fast through the column (tR < 3.75 min). At room temperature, the compound was susceptible to oxidation by hydrogen peroxide and transition metals. The ionogram of most of the stress solutions indicated the presence of a product having m/z 256, which might be a result of N- or Smethylation or -SH oxidation. The results of the study indicate that the method is selective, sensitive and suitable to be used for determination of OXCPM in bulk and under stress conditions.

Antibiotic resistance (AR) is one of the most serious global health issues today. Antibiotic abuse in the medical, veterinary, and agricultural industries, including incorrect antibiotic prescribing, overuse in the livestock industry, and poor cleanliness practices in hospitals, all contribute to the emergence of AR. Antibacterial drugs are derived from bacteria or molds or are synthesized de novo. In the present study, S‐substituted derivatives of 5‐(4‐methoxyphenyl)‐1,3,4‐oxadiazole‐2‐thiol (6 a‐p) were synthesized, fully characterized, and assessed for their inhibitory potential against various Gram‐negative and positive bacterial strains. The compounds demonstrated potent inhibition activity against all selected bacterial strains P. aeroginosa (−), E. coli (−), K. pneumonae (−), S. typhi (−), S. aureus (+), and B. subtilis (+) in comparison to standard ciprofloxacin drug. Among the synthesized derivatives, compounds 6 e and 6 o exhibited high selectivity and potency against the S. typhi (−) strain. The library 6 a‐o was also evaluated for in vitro chymotrypsin enzyme inhibitory activity, and all derivatives displayed weak inhibition potential in contrast to standard chymostatin (IC50 = 8.24±0.11 μM). Studies such as this one may aid in designing and discovering potential antibacterial agents for treating various bacterial infections. [ABSTRACT FROM AUTHOR]

Purpose: To synthesize a series of new 2-[2,3-dihydro-1,4-benzodioxin-6-yl(phenylsulfonyl)amino]-N- (un/substituted-phenyl) acetamides, and evaluate their anti-diabetic potentials. Methods: Synthesis of the parent compound N-(2,3-dihydro-1,4-benzodioxin-6-yl) benzenesulfonamide (3) was carried out by reacting 2,3-dihydro-1,4-benzodioxin-6-amine (1) with benzenesulfonylchloride (2) in aqueous basic medium under definite pH controls. After that 3 was further treated with various 2- bromo-N-(un/substituted-phenyl)acetamides (6a-l) to yield new compounds (7a-l) in polar aprotic solvent, DMF (dimethylformamide), using LiH as activator. The proposed structures of the synthesized compounds were confirmed using proton-nuclear magnetic resonance (¹H-NMR) and infra-red spectroscopy (IR), and CHN analysis. Their anti-diabetic potential was evaluated by α-glucosidase enzyme inhibitory studies. Results: All the new compounds demonstrated weak (7a-h, 7j and 7l) to moderate (7i and 7k) inhibitory activities against α-glucosidase enzyme. IC50 (50 % inhibition concentration) values for 7i and 7k were 86.31±0.11 μM and 81.12±0.13 μM, respectively relative to acarbose (reference standard) with IC50 of 37.38±0.12 μM. Conclusion: All the synthesized compounds have weak to moderate activity against α-glucosidase enzyme. These compounds can thus be considered as possible therapeutic entrants for type-2 diabetes. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the enzymetic, non-enzymetic toxicity and antioxidant potential of a drug candidate 5-Benzyl-1,3,4-Oxadiazole-2-Thiol(OXPA) using computational tools and in vivo models. The binding pattern of it, with different toxicity/oxidative enzymes was predicted using software pkCSM, Protox- II, LAZAR, Mcule 1-Click Docking 3D-Ligand binding Site and best score obtained used as an evaluating criterion. After acute oral toxicity, in vivo. antioxidant and hepato protective activity was investigated on male wistar rats, segregated into four groups as control (NS), toxic (INH-RIF), standard (Silymerin) and sample (OXPA, 100mg/Kg) for 21days. Level of antioxidant enzymes / histopathology and serum biochemical parameters in liver and blood of treated rats was assessed by using scientific tools. In silico study reveal no profound toxicity parameters however, LD50 found to be 560mg/Kg while in vivo study declared it safe till 1000mg/Kg, as having no toxicity symptoms. Molecular interaction score with GTH reductase, s-transferase and significant in vivo antioxidant effect on catalase, SOD, TBARS enzymes and histopathological assessment, declare OXPA a good antioxidant having significant (P< 0.05) hepato protective activity. Results of in silico, in vivo studies declare the propensity of 5-Benzyl-1, 3, 4-oxadiazole-2-thiol as potential antioxidant, for further investigations as a drug. [ABSTRACT FROM AUTHOR]

2-Furoyl-1-piperazine (1) was treated with a series of alkyl/aryl sulfonyl chlorides (2a-i) under benignant conditions to obtain its N-sulfonated derivatives (3a-i). These compounds were screened for their antibacterial potential against pathogenic bacteria. The low Minimum Inhibitory Concentration (MIC) values of these molecules, in comparison of ciprofloxacin, demonstrated their high antibacterial potential. Cytotoxic activities were ascertained through their hemolytic potential and mild hemolytic profiles of these compounds proved them to be promising compounds for drug designing and development. [ABSTRACT FROM AUTHOR]

The synthetic methodology was initiated by reacting 1,4-benzodioxane-6-amine (1) with 2-bromoacetyl bromide (2) in aqueous alkaline media under dynamic pH control to get compound 2,3-dihydro-1,4-benzodioxin-6-yl-2- bromoacetamide (3). In the subsequent reactions, a variety of un/substituted-benzoic acids (4a-k), through a succession of three steps, was converted into respective oxadiazole nucleophiles, 7a-k. Finally, the targeted molecules, 8a-k, were obtained by reacting 7a-k with electrophile 3 in an aprotic polar solvent. These compounds were corroborated by spectral characterization like IR, EI-MS, ¹H-NMR, and CHN analysis data. These molecules were screened for their antibacterial potential and most of them exhibited a potent activity. Moreover, their cytotoxicity was profiled through hemolytic activity and it was observed that majority of them was very modest in toxicity. [ABSTRACT FROM AUTHOR]

1,2,4-triazoles are a major group of heterocyclic compounds. In the current work, a concise library of such triazoles synthesized through a multistep protocol. The synthesis involved hydrazinolysis of ethyl-2-(p-Cl-phenoxy) acetate followed by reflux with phenyl isothiocyanate to yield the intermediate 2-[2-(p-Cl-phenoxy)acetyl)-N-phenylhydrazinecarbothioamide. This intermediate was then cyclized to form 5-[p-(Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol (the parent moiety) at alkaline pH. In parallel, 3-bromopropionyl bromide was reacted with a series of phenylamines to yield N-(substituted-phenyl)bromopropanamides. In the final step, N-substitution of 5-[p-(Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol was carried out with N-(substituted-phenyl)bromopropanamides to give desired library of 3-[5-[(p-Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-ylthio]-N-(substituted-phenyl) propanamides (8a-l). The prepared moieties were identified via IR, NMR, & EIMS and evaluated for urease and antiproliferative activities. 3-[5-[(p-Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-ylthio]-N-(3-methylphenyl) propanamide 8k, was found to be most prominent hit as urease inhibitor (IC50= 42.57± 0.13 µM) using thiourea as standard (IC50= 21.25±0.15µM). The interaction of 8k with urease were studied using docking studies. Antiproliferative activity results showed 8k as promising candidates and rest of the synthesized derivatives were found to be moderately anti-proliferative. Molecular docking results also displayed 8k, 8h, and 8c as potential hits for further study. [ABSTRACT FROM AUTHOR]

Our efforts lay emphasis on synthesis of S-aralkylated 5-(4-OMeC6H5)-4-phenyl-4H-1,2,4-triazol-3-thiols like pharmacologically active candidates to counter neurodegenerative disorder; Alzheimer's disease. A synthetic strategy was instigated by esterifying 4-methoxybenzoic acid through Fisher esterification's methodology. Hydrazinolysis of corresponding ester was performed under reflux with methanolic hydrated hydrazine to afford 4-methoxybenzohydrazide (I) which refluxing with phenyl isothiocyanate (II) in MeOH to yield a reactive intermediate (III). The later underwent base-catalyzed intermolecular cyclization to furnish 5-(4-OMeC6H5)-4H-1,2,4-triazol-3-thiol (IV). Ultimately, IV was aralkylated at thiol position with aralkyl halides V(a-l) in polar aprotic solvent and catalytic amounts of LiH to provide S-aralkylated 5-(4-OMeC6H5)-4-phenyl-4H-1,2,4-triazol-3-thiols VI(a-l). Modern spectral analysis data explicitly established all the substitutions on nucleophilic S-atom of parent 1,2,4-triazol-3-thiol ring. Effective anti-cholinesterase potential depicted in 3-(phenylpropylthio)-5-(4-OMeC6H5)-4-phenyl-4H-1,2,4-triazole; VIc (IC50; 3.26±0.35 µM) against acetyl cholinesterase; AChE and 3-(phenethylthio)-5-(4-OMeC6H5)-4-phenyl-4H-1,2,4-triazole; VIb (IC50; 8.52±0.54 µM) against butyrylcholinesterase; BChE enzyme as compared to standard Eserine for both enzymes (IC50; 0.04±0.01 µM). Molecular modelling analyses had been conducted to recognize the interconnection of these compounds with enzymes that suggested key interactions (Docking is made to untie the active binding sites). Anti-proliferative activity results showed VIg and VIj with -Cl groups on benzylic ring as promising candidates with HCT-116 cell viability of 14.83 % and 3.09 % respectively. [ABSTRACT FROM AUTHOR]