Synthesis, structure, and antifungal evaluation of some novel 1,2,4-triazolylmercaptoacetylthiosemicarbazide and 1,2,4-triazolylmercaptomethyl-1,3,4-thiadiazole analogs.

Novel 1-[[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptoacetyl]-4-alkyl/aryl-3-thiosemicarbazides (5-12) were synthesized by the reaction of 4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-ylmercaptoacetylhydrazide (4) with substituted isothiocyanates. Cyclodehydration of thiosemicarbazides with concentrated sulfuric acid yielded 2-[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptomethyl-5-alkyl/arylamino-1,3, 4-thiadiazoles (13-17). The new compounds were evaluated for in vitro antifungal activity using the microdilution method. The tested compounds showed varying degrees of activity against Microsporum gypseum NCPF-580, Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans ATCC 10231 (MIC 8-4 microg/mL).

Synthesis and structure-antituberculosis activity relationship of 1H-indole-2,3-dione derivatives.

New series of 5-fluoro-1H-indole-2,3-dione-3-thiosemicarbazones 2a-k and 5-fluoro-1-morpholino/piperidinomethyl-1H-indole-2,3-dione-3-thiosemicarbazones 3a-r were synthesized. The structures of the synthesized compounds were confirmed by spectral data, elemental and single crystal X-ray diffraction analysis. The new 5-fluoro-1H-indole-2,3-dione derivatives, along with previously reported 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 2l-v, 1-morpholino/piperidinomethyl-5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones 4a-l, and 5-nitro-1H-indole-2,3-dione-3-[(4-oxo-1,3-thiazolidin-2-ylidene)hydrazones] 5a-s, were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv. Among the tested compounds, 5-nitro-1H-indole-2,3-dione-3-thiosemicarbazones (2p, 2r, and 2s) and its 1-morpholinomethyl derivatives (4a, 4e, 4g, and 4i) exhibited significant inhibitory activity in the primary screen. The antituberculosis activity of molecules with diverse skeletons was investigated by means of the Electronic-Topological Method (ETM). Ten pharmacophores and ten anti-pharmacophores that have been found by this form the basis of the system capable of predicting the structures of potentially active compounds. The forecasting ability of the system has been tested on structures that differ from those synthesized. The probability of correct identification for active compounds was found as equal to 93% in average. To obtain the algorithmic base for the activity prediction, Artificial Neural Networks were used after the ETM (the so-called combined ETM-ANN method). As the result, only 9 pharmacophores and anti-pharmacophores were chosen as the most important ones for the activity. By this, ANNs classified correctly 94.4%, or 67 compounds from 71.

Synthesis and anticancer evaluation of some new hydrazone derivatives of 2,6-dimethylimidazo[2,1-b][1,3,4]thiadiazole-5-carbohydrazide.

In this study, some novel 2,6-dimethyl-N'-substituted phenylmethylene-imidazo[2,1-b][1,3,4]thiadiazole-5-carbohydrazides (3a-3h) were synthesized from 2,6-dimethylimidazo-[2,1-b][1,3,4]thiadiazole-5-carbohydrazide (2). The newly synthesized compounds (3a-3h) were evaluated in the National Cancer Institute's 3-cell line, one dose in vitro primary cytotoxicity assay. Compounds 3c and 3h which passed the criteria for activity in this assay (20-29% growth percentages) were scheduled automatically for evaluation against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions. Sulforhodamine B (SRB) protein assay was used to estimate cell stability or growth. 2,6-Dimethyl-N'-(2-hydroxyphenylmethylidene)imidazo[2,1-b][1,3,4]thiadiazole-5-carbohydrazide (3c) showed the most favorable cytotoxicity. This compound demonstrated the most marked effects in the National Cancer Institute's 60 human tumor cell line in vitro screen on an ovarian cancer cell line (OVCAR log(10)GI(50) value -5.51).

Synthesis and primary cytotoxicity evaluation of 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1H-2-indolinones.

New esters (2b and 2c) and hydrazides (3b and 3c) were synthesized from 6-methyl/fluoro-3-phenyl-4(1H, 3H)-quinazolinone-2-thiones (1b and 1c). Subsequent treatment of 3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetic acid hydrazides (3a-e) with 1H-indole-2,3-diones (4a-e) furnished the corresponding 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1H-2-indolinones (5a-u). The structures of new compounds were determined by analytical and spectral (IR, 1H-NMR, (13)C-NMR, EIMS) methods. Previously reported 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-bromo-1H-2-indolinone 5v and compounds 5b, 5d and 5o chosen as prototypes were evaluated against the full panel of 60 human tumour cell lines at a minimum of five concentrations at tenfold dilutions in the National Cancer Institute in vitro primary cytotoxicity assay. Sulforhodamine B protein assay was used to estimate cell stability or growth. 3-[[(6-Chloro-3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-fluoro-1H-2-indolinone 5o showed the most favourable cytotoxicity against a renal cancer cell line UO-31 (log(10)GI(50) value -6.68). Compound 5v was also tested against human immunodeficiency virus 1 (HIV-1). Compound 5v was confirmed moderately active against HIV-1.

Synthesis and antimicrobial activity of [2-[2-(N, N-disubstituted thiocarbamoyl-sulfanyl)-acylamino] thiazol-4-yl]acetic acid ethyl esters.

[2-[2-(N, N-Disubstituted thiocarbamoyl-sulfanyl)acylamino ]thiazol-4-yl]acetic acid ethyl esters (3a-x) were synthesized by the reaction of potassium salts of N, N-disubstituted dithiocarbamoic acids with [2-(2-chloroalkanoyl)amino-thiazol-4-yl]acetic acid ethyl esters. The structures of the synthesized compounds were confirmed by elemental analyses, UV, IR, (1)H-NMR, and EI mass spectral data. The antimicrobial activities of all the compounds were investigated by microbroth dilution technique using Mueller-Hinton broth and Mueller-Hinton agar. In this study, Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa AT CC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153 and Candida albicans ATCC10231 were used as test microorganisms. Among the tested compounds 3a, d, e, f, h, k, w activity against S. epidermidis ATCC 12228 (MIC: 156 mg/L, 78 mg/L, 62.5 mg/L, 78 mg/L, 62.5 mg/L, 312 mg/L, 250 mg/L, respectively), compound 3d had some activity against S. aureus ATCC 6538 (MIC: 156 mg/L) and C. albicans ATCC 10231(MIC: 156 mg/L). Compounds 3l, 3x also evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system and BACTEC 12B medium. The preliminary results indicated that all of the tested compounds were inactive against the test organism.

Synthesis and primary cytotoxicity evaluation of new 5-bromo-3-substituted-hydrazono-1H-2-indolinones.

In this study a new series of 5-bromo-3-[(3-substituted-5-methyl-4-thiazolidinone-2-ylidene)-hydrazono]-1H-2-indolinones (3a-i) and 5-bromo-3-[(2-thioxo-3-substituted-4, 5-imidazolidinedione-1-yl)imino]-1H-2-indolinones (4a-f) was synthesized by the cyclization of 5-bromo-3-(N-substituted-thiosemicarbazono)-1H-2-indolinones (2a-i)with ethyl 2-bromopropionate in anhydrous ethanolic medium and oxalyl cloride in anhydrous diethyl ether, respectively. Six compounds chosen as prototypes were evaluated in the 3-cell line, one dose in vitro primary cytotoxicity assay. Four of them were evaluated against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions. Among the compounds tested, the 4-fluoro-phenylthiosemicarbazone derivative 2f showed the most favorable cytotoxicity. This compound demonstrated the most marked effects on a breast cancer cell line (BT-549, log(10)GI(50) value -6.40), a non small cell lung cancer cell line (NCI-H23, log(10)GI(50) value -6.10), and an ovarian cancer cell line (IGROV1, log(10)GI(50) value -6.02).