Validated Stability-Indicating Method for Alendronate Sodium Employing Zwitterionic Hydrophilic Interaction Chromatography Coupled with Charged Aerosol Detection

Alendronate sodium is widely used in the treatment of osteoporosis and Paget’s disease. The HPLC method development for alendronate sodium, in particular, is challenging owing to the absence of chromophoric group and its high polarity. In the present study, a short and simple isocratic method was developed involving hydrophilic interaction liquid chromatography, coupled with a charged aerosol detector. The developed method was validated according to the ICH Q2(R1) guideline and was successfully applied for the analysis of a marketed formulation containing the drug.

     

Synthesis of 2,3-dihydroquinazolin-4(1H)-ones from anthranilamide and ketones over Hβ zeolite in aqueous media*

The synthesis of 2,3-dihydroquinazolin-4(1H)-ones by cyclocondensation of anthranilamide with ketones in aqueous media using Hβ zeolite is reported. The scope of the reaction was explored by various ketones such as aromatic, aliphatic and cyclic ketones. Based on the preliminary mechanistic results, a tentative mechanism for the formation of 2,3-dihydroquinazolin-4(1H)-ones using zeolite catalyst (Hβ) is predicted. The reusability study, large-scale experiment and water as solvent showed significant benefits of this catalytic protocol in comparing to earlier methods.     

Synthesis of Novel Fused Thiazolo[3,2‐a]pyrimidin‐3‐ols and Evaluation for their Antibacterial Activity

A series of novel fused thiazolo[3,2‐a]pyrimidin‐3‐ol derivatives have been synthesized by reaction of fused pyrimidine‐thiones with 4‐substituted phenacyl bromide/3(2‐bromoacetyl)coumarin in refluxing acetic acid with good yields. All the synthesized compounds were confirmed by spectral studies and screened for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus thuringiensis (Gram positive), Escherichia coli, and Klebsiella pneumoniae (Gram negative) bacterial strains. Activity results revealed that all the compounds were weak to good active against the tested bacterial strains on comparing with the standard drug gentamicin.     

1-Sulfopyridinium chloride:Green and expeditious ionic liquid for the one-pot synthesis of fused 3,4-dihydropyrimidin-2(1H)-ones and thiones under solvent-free conditions

1-Sulfopyridinium chloride portrayed as an efficient and recyclable ionic liquid for the synthesis of fused3,4-dihydropyrimidin-2(1H)-ones and thiones via a modified Biginelli reaction involving one-pot three component condensation of 6-methoxy-1-tetralone,arylaldehydes and urea/thiourea under solventfree conditions.Analytically pure products are formed within 10–20 min in excellent yields.     

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.     

Catalyst-free synthesis of amines from cyclic ketones and formamides in superheated water

A novel and environmentally benign protocol for the synthesis of amines from cyclic ketones and formamides is demonstrated. The reaction proceeds under catalyst-free and superheated water conditions and yields range from poor to excellent.     

Synthesis,biological evaluation,and docking study of a series of 1,4-disubstituted 1,2,3-triazole derivatives with an indole-triazole-peptide conjugate

A series of new compounds containing an indole-triazole - peptide conjugate were designed as potential agents possessing the dual anti-bacterial and anticancer activities. Accordingly, 20 compounds were prepared via a multi-step synthesis involving the copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in moderate to high yield. All the synthesized compounds were purified by chromatographic techniques and characterized by IR, ¹H and ¹³C NMR and mass spectral data. The synthesized derivatives were screened for their antimicrobial activities against one gram-positive (Staphylococcus aureus) and three gram-negative (Escherichia coli, Klebsiella pneumonia, and Proteus vulgaris) bacteria using an agar-well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the strains. The potential of DNA gyrase inhibitory activity of this compound was assessed by using molecular docking studies in silico carried out using Autodock Vina software. The low ΔG_bind value (−9.4 Kcal/mol) of compound 9e suggested its good interactions with the target protein in silico. The cytotoxic activities of some of the compounds synthesized were evaluated via a MTT assay using the human lung cancer cell line A549. Several compounds showed promising activities among which compound 9b , 9k, and 9e showed low IC₅₀ values.     

Synthesis and Biological Evaluation of New Ibuprofen‐1,3,4‐oxadiazole‐1,2,3‐triazole Hybrids

A new hybrid polydentate template comprising distinctive pharmacophoric groups, namely, ibuprofen, 1,3,4‐oxadiazole, and 1,2,3‐triazole linked through a thioether bridge was achieved by one‐pot synthesis by exploring multicomponent Cu‐catalyzed “click chemistry” approach. The target structures were characterized by NMR, IR, and LC‐Mass. The X‐ray analysis of 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐(3‐nitrophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole ( 8a ) confirmed the assigned structure. The in vitro antibacterial and anticancer activity of these compounds revealed that 2‐(1‐(4‐isobutylphenyl)ethyl)‐5‐(((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐1,3,4‐oxadiazole ( 8b ) demonstrated more potent antibacterial activity against Gram‐negative strains (Escherichia coli and Pseudomonas aeruginosa) and 2‐(((1‐(2,4‐dimethylphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl)thio)‐5‐(1‐(4 isobutylphenyl)ethyl)‐1,3,4‐oxadiazole ( 8e ) exhibited anticancer activity with IC₅₀ of 27.50 and 31.03 μg/mL against HeLa and MCF‐7 cell lines, respectively.     

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).