ChemInform Abstract: Synthesis and Evaluation of Some Novel Substituted 1,3,4-Oxadiazole and Pyrazole Derivatives for Antitubercular Activity (original) (raw)
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Objective: The objective of the paper was to synthesize and characterize new derivatives of thiazole-based pyrazole derivatives and evaluate them for the antitubercular activity. Material and methods: The pyrazole derivatives have been synthesized by the two steps process in that first step pyrazole based carbothioamide compounds was synthesized and it further reacted with 3-(2-bromoacetyl)-2Hchromen-2-one to from the final compounds. Total Fourteen compounds have been synthesized and characterized by IR, 1 HNMR, elemental analysis and mass spectral analysis. The final Compounds (TP-1 to TP-14) have been evaluated for antitubercular activity by two Ex-vivo method i.e. LRP assay and MABA method. Result and Discussion: IR analysis of compound TP-1 to TP-14 showed the occurrence of the characteristics peak at 3415-3420 (-NH), 1717-1721 (-C=O) and 1627 (-C=N). The 1H-NMR spectrum shown a singlet peak at δ 8.53, due to the chromen-2-one-4H proton. The characteristic peak of-NH proton was attributed at δ 12.02-12.03. The MABA method depicted the efficacy of compound by MIC value in µg/ml; five compounds i.
Research Paper Synthesis And Antitubercular Activity of 1,3,4-Oxadiazoles Clubbed With Pyrroles
2013
Mycobacterium tuberculosis causes a serious health problem globally. In the p resent study, we enlighten the synthesis of molecularly diverse 1,3, 4-oxadiazole in conjunction with substituted 1 H- pyrrole motif. The resulting structural diversity w as screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37 Rv strains. The analogs, such as 2c, 2i, 2k, and 2m were found promising against H 37 Rv strains up to <6.25 µM MIC value. However, further exploration and modification are essential in a search for drug lik e hint .
A number of pyrazole-oxadiazole conjugates were synthesized and evaluated for their ability to function as antiproliferative agents on various human cancer cell lines. These conjugates comprise of pyrazole and 10 oxadiazole scaffolds closely attached to each other without any spacer as two structural classes. Type I class has a trimethoxy substituent and the type II class has 3,4-(methylenedioxy) substituent on their A rings. Among these conjugates 11a, 11d and 11f manifest potent cytotoxicity with IC50 values ranging from 1.5 μM to 11.2 μM apart from inhibition of tubulin polymerization with the IC50 values 1.3μM, 3.9μM and 2.4μM respectively. Cell cycle assay showed that treatment with these conjugates result in 15 accumulation of cells in G2/M phase and disrupt microtubule network. Elucidation of Zebrafish embryos revealed that the conjugates cause developmental defects. Molecular docking simulations determined the binding modes of these potent conjugates at the colchicine site of tubulin.
In search of more potent and safe new antitubercular agents, here new 2-pyridinyl substituted thiazolyl-5-aryl-1,3,4-oxadiazoles (6a–o), have been designed and synthesized using thionicotinamide as a starting, following novel multistep synthetic route. An intermediate, pyridinyl substituted thiazolyl acid hydrazide (4) when condensed with benzoic acids/nicotinic acids (5a–o) in the presence of silica supported POCl 3 yielded better to excellent yields of the title compounds. All the synthesized compounds (6a–o) and intermediate acid hydrazide (4) have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG. Amongst them, 6f, 6j, 6l and 6o have revealed promising activity against M. bovis BCG at concentrations less than 3 lg/mL. These compounds have shown low cytotoxicity (CC 50 : >100 lg/mL) towards four human cancer cell lines. Molecular docking study has also been performed against mycobacterial enoyl reductase (InhA) enzyme to gain an insight into the binding modes of these molecules and recorded good binding affinity. The ADME properties the title products have also been analyzed.
International Journal of Scientific Research in Science and Technology, 2022
Heterocyclic compounds possess diverse biological properties that have led to intense study and research of these compounds. One of these compounds is Oxadiazole which has been found to exhibit various pharmacological activities. 1,3,4-oxadiazole having heterocyclic nucleus is a novel molecule which attract the chemist to search a new therapeutic molecule. Research on 1,3,4-oxadiazole and their synthetic analogues have revealed a variety of pharmacological activities including anti-microbial, anti-tubercular and insecticidal agents. Some of these compounds have also analgesic, anti-inflammatory, anti-cancer, anti-HIV agent, anti-parkinsonian and anti-proliferative agent. It was our interested to make novel derivatives of the titled compounds and evaluate the anti-tubercular activities. 1,3,4-oxadiazole and its derivatives (4a-4e) were obtained. The current study discusses the microwave irradiation synthesis of derivatives with the goal of generating new medications with high specificity for mycobacterium tuberculosis and low harm to the human.
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.