thiourea and 1-2-4-triazole

Two series of 1,3,4-thiadiazole (40a-o) and 1,2,4-triazole-5-thione (41a-l) derivatives bearing a 2-pentyl-5-phenyl-1,2,4-triazole-3-one ring were synthesized and then studied for their urease inhibitory activities using thiourea as a standard drug. Among the two groups, the first group (40a-o) did not show good activity while the second group (41a-l) showed excellent activity. Compound 41j (1091.24 ± 14.02 µM) of the second series of compounds showed lower activity than thiourea, while the remaining 11 compounds (41a-i, k, and l) showed better activity than thiourea (183.92 ± 13.14 µM). Among the 11 compounds, 41b (15.96 ± 2.28 µM) having the 3-F group on the phenyl ring showed the highest inhibitory activity. Urease kinetic studies of 41b, which is the most active compound, determined it to have an un-competitive inhibition potential. Moreover, in silico analysis against urease from jack bean with 27 new heterocyclic compounds and the reference molecule was carried out to see the necessary interactions responsible for urease activity. The docking calculations of all compounds supported stronger binding to the receptor than the reference molecule, with high inhibition constants. In addition, compound 40m was characterized by single-crystal X-ray diffraction analysis. X-ray analysis reveals that the structures of the compound 40m crystallize in the monoclinic P21/c space group with the cell parameters: a = 10.2155(9) Å, b = 22.1709(18) Å, c = 21.4858(17) Å, β = 99.677(8)°, V = 4797.0(7) Å

Topics: Enzyme Inhibitors; Kinetics; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship; Thiones; Thiourea; Urease

Topics: A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Drug Screening Assays, Antitumor; G1 Phase Cell Cycle Checkpoints; Humans; MCF-7 Cells; Mice; Structure-Activity Relationship; Thiourea; Triazoles; Urea

Thirty six novel heterocyclic derivatives of ethyl 2-(2-pyridylacetate) were efficiently synthesized. The new compounds involve the linkage of a 2-pyridyl ring with thiosemicarbazide (compounds

Topics: Anti-Infective Agents; Bacteria; Cell Line; Cells, Cultured; Crystallography, X-Ray; Fungi; HIV-1; Humans; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Oxadiazoles; Structure-Activity Relationship; Thiadiazoles; Thiourea; Triazoles

In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a-d), 4-alkyl/aryl-2,4-dihydro-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-3H-1,2,4-triazole-3-thiones (3a-n), and 2-alkyl/arylamino-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-1,3,4-thiadiazoles (4a-g). The newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR (APT), mass and elemental analysis. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, Trichophyton mentagrophytes var. erinacei NCPF 375, Microsporum gypseum NCPF 580, and T. tonsurans NCPF 245. 3c, 3f, 3m, 3n, and 4e showed the highest antibacterial activity. Particularly 3c, 3f, 3g, 3k, 3n, 4a, 4e, and 4g showed the highest antifungal activity against tested fungi.

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Dose-Response Relationship, Drug; Fungi; Hydrazines; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Thiadiazoles; Thiourea; Triazoles

Some new structural type inhibitors of urease, i.e. 2,5-disubstituted-1,3,4-oxadiazoles (4a-e) and 4,5-disubstituted-1,2,4-triazole-3-thiones (5a-e) were synthesized in two steps from mandelic acid hydrazides (2a-e) and aryl isothiocyanates. The hydrazides in turn were synthesized from mandelic acid via esterification. Compounds 4a-e and 5a-e were evaluated against jack bean urease. Compounds 4d, 5b, and 5d were found to be more potent, with IC(50) values of 16.1 +/- 0.12 microM, 18.9 +/- 0.188 microM, and 16.7 +/- 0.178 microM, respectively, when compared to the standard (thiourea; IC(50) = 21.0 +/- 0.011 microM). These compounds may be subjected to further investigations for the development of antiulcer drugs.

Topics: Anti-Ulcer Agents; Drug Design; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Mandelic Acids; Oxadiazoles; Structure-Activity Relationship; Triazoles; Urease