Synthesis of novel substituted pyrazolyl-2-toluidinomethanethione and pyrazolyl-2-methoxyanilinomethanethione as potential antitubercular agents (original) (raw)
Related papers
Acta poloniae pharmaceutica
A series of amino-5-[(substituted) phenyl]-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H- 1-pyrazolylmethanethione were synthesized by the reaction between thiosemicarbazide and chalcones and were tested for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv and INH resistant Mycobacterium tuberculosis using bactec method. Among the synthesized compounds, compound (4b), amino-5-(4-chlorophenyl)-3-(4-hydroxy-3-methylphenyl)-4, 5-dihydro-H-1-pyrazolylmethanethione was found to be the most active agent against Mycobacterium tuberculosis H37Rv (MTB) and INH resistant Mycobacterium tuberculosis (INHR-MTB) with minimum inhibitory concentration of 0.43 microM . When compared to INH-compound (4b) was found to be 1.62 fold and 26.41 fold more active against MTB and INHR-MTB, respectively.
Bioorganic & Medicinal Chemistry Letters, 2006
A series of amino-5-[(substituted) phenyl]-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione were synthesized by the reaction between thiosemicarbazide and chalcones and were tested for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H 37 R v and INH resistant Mycobacterium tuberculosis using bactec method. Among the synthesized compounds, compound (4b), amino-5-(4-chlorophenyl)-3-(4-hydroxy-3-methylphenyl)-4,5-dihydro-1H-1-pyrazolylmethanethione was found to be the most active agent against Mycobacterium tuberculosis H37 Rv (MTB) and INH resistant Mycobacterium tuberculosis (INHR-MTB) with minimum inhibitory concentration of 0.43 µM . When compared to INH-compound (4b) was found to be 1.62 fold and 26.41 fold more active against MTB and INHR-MTB, respectively.
European journal of …, 2009
In the present investigation, a series of 1-isonicotinoyl-3-methyl-4-(2-(substitutedphenyl)hydrazono)-1H-pyrazol-5(H)-ones were synthesized by the reaction between isonicotinohydrazide with substituted ethylacetoacetate derivatives using acetic acid as solvent which yielded substituted pyrazol-5(H)-one derivatives. Newly synthesized compounds were tested for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system. Among the synthesized compounds, 4-(2-(2,6-dichlorophenyl)hydrazono)-1-isonicotinoyl-3-methyl-1H-pyrazol-5(4H)-one and 4-(2-(1-isonicotinoyl-3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)hydrazinyl) benzene-sulfonamide were found to be more active agent against M. tuberculosis H37Rv with minimum inhibitory concentration of 0.0034, 0.0032 µM at actual MIC 1.66 and 1.64 µg/mL, respectively. Isonicotinohydrazide Pyrazol-5(H)-ones Anti-tubercular activity Anti-mycobacterial activity Mycobacterium tuberculosis M. tuberculosis H37Rv
Bioorganic & medicinal …, 2008
Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC = 4 lg/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity.
Bioorganic & medicinal …, 2009
Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC = 4 lg/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity.
Beni-Suef University Journal of Basic and Applied Sciences, 2015
Emergence of multi-drug resistant tuberculosis (MDR-TB) and HIV-TB co-infections potentiate the development of newer antitubercular agents to combat against tuberculosis, a dreadful disease. In the present investigation a series of pyrazoline analogues were designed and synthesized based on the structure of known antitubercular agent thiacetazone, in hope of obtaining new and safe antitubercular agents. The target molecules were synthesized in two steps, starting with the condensation of 4-aminoacetophenone and panisidine in methanolic sodium hydroxide solution followed by the cyclization of intermediate chalcones with appropriate semicarbazide/thiosemicarbazide in glacial acetic acid. All the synthesized compounds were characterized by 1 H NMR, IR and mass spectral data and the purity of the compounds was checked by elemental analysis. Their antimycobacterial activity was evaluated by two folds serial dilution method. 3-(4-Aminophenyl)-N-(4-chlorophenyl)-4,5-dihydro-5-(4-methoxyphenyl)pyrazole-1carboxamide (4i) showed maximum activity against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of 7.41 mM.
Journal of Antimicrobial Chemotherapy, 2007
The objective of this work was to synthesize 15 new 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea compounds and evaluate their in vitro and in vivo antimycobacterial activities. Methods: 5-Cyclobutyloxazol-2-amine was reacted with 1,1 0-thiocarbonyldiimidazole, followed by various substituted anilines and 2-amino pyridines to yield the 15 compounds, which were subjected to in vitro and in vivo evaluation against Mycobacterium tuberculosis H37Rv (MTB) and a clinical isolate of multidrug-resistant M. tuberculosis (MDR-TB). Results: Among the 15 compounds screened, 7 compounds inhibited both MTB and MDR-TB in vitro with MICs of <1 mM. In the in vivo screening, compound 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3-(2 0-trifluoromethyl)phenylthiourea (compound 8) was equally active as isoniazid at the same dose level. Conclusions: Compound 8 was found to be the most active, with an in vitro MIC of 0.14 mM and was 2.5 and 80 times more active than isoniazid against MTB and MDR-TB, respectively. Compound 8 was non-toxic to Vero cells up to 183 mM, with a selectivity index of >1307. In the in vivo animal model, compound 8 decreased the mycobacterium load in lung and spleen tissues with 2.8 and 3.94 log 10 reductions, respectively.
The purpose of this study was to prepare various 1-((1-(substituted)-1H-1,2,3-triazol-4-yl)methyl)-N,3-diphenyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxamides using click chemistry. The synthesized compounds were characterized using various analytical techniques like NMR spectroscopy, mass spectrometry, and elemental analysis and screened for in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv strain and two 'wild' strains Spec. 210 and Spec. 192 using a classical test-tube method of successive dilution in Youmans' modification of the Proskauer and Beck liquid medium and were evaluated for a MTB pantothenate synthetase (PS) inhibition study as well. The final analogues exhibited minimum inhibitory concentration ranging from 24.72 to 4200 mM. Among the compounds, 1-((1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-N,3-diphenyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxamide (7d) was found to be the most active compound with IC 50 1.01 AE 0.32 mM against MTB PS; it inhibited MTB with MIC 24.72 mM and it was non-cytotoxic at 50 mM in the RAW 267 cell line. Further, 7d was docked into the crystal structure of MTB PS to investigate its binding interaction pattern.
Thiazolyl-pyrazole derivatives as potential antimycobacterial agents
Bioorganic & Medicinal Chemistry Letters, 2019
Mycobacterium tuberculosis (Mtb) is an obligate aerobe that is capable of long-term persistence under conditions of low oxygen tension. A series of thiazolyl-pyrazole derivatives (6a-f, 7a-f, 8c, 8e) were screened for antimycobacterial activity against dormant M. tuberculosis H37Ra (D-MTB) and M. bovis BCG (D-BCG). Nine thiazolyl-pyrazole analogs, 6c, 6e, 7a,7b, 7c, 7e, 7f, 8c and 8e exhibited promissing minimum inhibitory concentration (MIC) values (0.20-28.25 µg/mL) against D-MTB and D-BCG strains of Mtb. Importantly, six compounds (7a, 7b, 7e, 7f, 8c and 8e) exhibited excellent antimycobacterial activity and low cytotoxicity at the maximum evaluated concentration of >250 µg/mL. Finally, the promising antimycobacterial activity and lower cytotoxicity profile suggested that, these compounds could be further subjected for optimization and development as a lead, which could have the potential to treat tuberculosis.