ChemInform Abstract: Synthesis and Evaluation of Some Novel Substituted 1,3,4-Oxadiazole and Pyrazole Derivatives for Antitubercular Activity (original) (raw)
2010
series of 5-{3’-oxo-6’-(substituted aryl)-2’,3’, 4’, 5’-tetrahydropyridazin-2’-yl methyl}-2- substituted 1,3,4-oxadiazole has been synthesized. Appropriate aromatic hydrocarbon reacts with succinic anhydride in presence of AlCl3 to yield β-Aroyl propionic acid (1a). The corresponding acid is cyclised with hydrazine hydrate to give 6-(substituted aryl)-2,3,4,5- tetrahydro-3-pyridazinone (1b).This intermediate after reaction with ethyl bromo acetate, hydrazinolysed into 3-oxo-6-(substituted aryl)-2, 3, 4, 5-tetrahydropyridazinyl acetohydrazide (1c).The resulting product was converted into 5-{3’-oxo-6’-(substituted aryl)-2’,3’,4’,5’- tetrahydropyridazin-2’-yl methyl}-2-substituted 1,3,4-oxadiazole. All the final compounds have been structurally elucidated on the basis of IR, 1H-NMR, mass spectral data and elemental analysis and screened for antitubercular activity
2010
In the development of organic therapeutic agents, pharmaceutical scientists have explored numerous approaches in finding and developing organic compounds that are now available to us in dosage forms suitable for the treatment of our ills and often for the maintenance of our health. The present work deals with evaluation of anti-tubercular activity of various aldehyde derivatives synthesized by Claisen-Schmidt condensation method. The formation of pyrazole derivatives by reaction with phenyl isothiocyanate was also attempted. The synthesized derivatives were screened for anti-tubercular activity and the compounds demonstrated some remarkable features to be actively considered as anti-tubercular drugs.
The synthesis of 2-furyl-5-(substituted)-1,3,4-oxadiazoles was carried out by microwave irradiation of 2-furoic acid and ethanol followed by subsequent hydrazinolysis with hydrazine hydrate. Finally furan-2-acid hydrazide was treated with appropriate carboxylic acid in the presence of phosphorous oxychloride to produce title compounds. The structures of the newly synthesized compounds were established on the basis of spectral analysis such as IR, H 1 NMR and Mass spectral data. The synthesized compounds were screened for their anti-tubercular activity.
Research on Chemical Intermediates, 2018
To fulfil the development goals towards the synthesis of innovative, potent and highly effective antimicrobial and antimycobacterial agents, a set of benzene sulfonamide pyrazole thio-oxadiazole derivatives (6a-6l) have been synthesized by the reaction of 4-[5-(3-fluoro-4-methoxyphenyl)-3-(5-mercapto-1,3,4oxadiazol-2-yl)-1H-pyrazol-1-yl]benzenesulfonamide with alkyl/aryl halides, identified by IR, NMR (1 H, 13 C, 19 F) and MS data. Composed compounds were examined for their antimicrobial and antitubercular activity. Antibacterial activity of compounds 6c, 6d, 6j and 6l was found promising against E. coli, P. Aeruginosa, S. Aureus and S. Pyogenes as compared to standard ampicillin. Compounds 6d, 6e, 6g, 6h and 6i were found active against tubercular strain H37Rv. Molecular docking studies against mycobacterium tuberculosis b-ketoacyl-acyl carrier protein synthase A (Kas-A) was carried out which suggests a possible mode of inhibition for this target protein and the potential of synthesized compounds as antitubercular agents.
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.
A number of novel 2-aryl substituted benzothiazoles were created for the current investigation, and their ability to suppress the growth of Mycobacterium TB H37Rv strain of the bacteria was assessed. FTIR and NMR spectral analysis were used to characterise the structures of the newly synthesised substances. The majority of the synthetic molecules exhibited good to moderate anti-tubercular efficacy. According to the findings, three compounds-3a, 3d, 3f, and 3g-have antitubercular activity that is either superior to or equal to that of ordinary streptomycin and pyrazinamide. Benzothiazoles should be given further thought as potential antitubercular drugs based on future research.
Synthesis and biological potentials of some new 1,3,4-oxadiazole analogues
Medicinal Chemistry Research, 2017
In continuation of our research to explore new antiproliferative agents, we report herein the synthesis and antiproliferative activity of two new series of N-(substituted phenyl)-5-aryl-1,3,4-oxadiazol-2-amine (4a-j) and N-{[5aryl-1,3,4-oxadiazol-2-yl]methyl}-substituted aniline (4k-t) analogs. The antiproliferative activity of fifteen compounds (4a-h, and 4n) was tested against nine different panels of nearly 60 NCI human cancer cell lines. N-(2-Methoxyphenyl)-5-(4-chlorophenyl)-1,3,4-oxadiazol-2-amine (4b) and 4-{5-[(2-Methoxyphenyl)amino]-1,3,4-oxadiazol-2-yl} phenol (4c) showed maximum antiproliferative activity among the series with a mean growth percents (GPs) of 45.20 and 56.73, respectively. The compound 4b showed significant percent growth inhibitions (GIs) on nearly 47 cancer cell lines and were found to have higher sensitivity towards HL-60(TB), MDA-MB-435, OVCAR-3, and K-562 with percent GIs (GIs) of 109.62, 105.90, 91.94, and 88.30, respectively. Similarly the compound, 4c showed significant percent GIs on nearly 42 cancer cell lines and were found to have higher sensitivity towards UO-31, MDA-MB-435, KM12, and K-562 with %GIs of 84.31, 80.52, 78.65, and 77.06, respectively. Both the compounds 4b and 4c showed better antiproliferative activity than the standard drug Imatinib while the antiproliferative activity of compound 4b was found to be nearly comparable to the standard drug 5-flurouracil (5-FU). The antiproliferative activity of five compounds (4o-s) was tested against the breast cancer cell lines (MCF-7 and MDA-MB-231) as per Sulforhodamine B assay (SRB assay). N-{[5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]methyl}-4-methylaniline (4p) was found to have significant antiproliferative activity against MCF-7 and MDA-MB-231 with GI 50 of 12.9 and 59.3 µM, respectively. Further, the free radical scavenging activity results were significant for the most active compounds, 4b (IC 50 = 21.07 µM) and 4c (IC 50 = 15.58 µM). The docking studies was also carried against tubulin enzyme and the most active compound (4b) showed good interaction with the residues Lys254, Ala250, Cys241, Val318, Ala316, Asn258, and Lys352 present in the hydrophobic cavity of tubulin.
2016
A number of substituted pyrazolidin-3-one, aryl oxadiazole and mercapto oxadiazoles are known for their biological importance like anti-bacterial, antitubercular, antioxidant and antiinflammatory activity. The present investigation is carried for the synthesis of certain substituted pyrazolidin-3-one, aryl oxadiazole and mercapto oxadiazole and carried out their biological activity. The title compounds has been synthesized from diclofenac acid & ofloxacin reacts with ethanol in presence of acid to give hydrazide which on further reaction with Ethylacetoacetate gives substituted pyrazolidin-3-one which undergoes Mannich reaction gives Pyrazolidin-3-one. Acid hydrazide on treatment with Aromatic acids in presence of Phosphorus oxychloride gives aryl oxadiazoles. Mercaptooxadiazoles synthesized using acid hydrazide and carbon disulphide. The newly synthesized compounds have been characterized by IR, 1 H NMR and CHN analysis. Selected compounds are screened for antimicrobial, antioxidan...