Search

A series of 2-aryl-5-[4-(1H-pyrrol-1-yl)phenyl]-1,3,4-oxadiazole derivatives (VIa-g) have been synthesized in good yields. These compounds were synthesized with an approach to reduce the growing anti-tubercular resistance and to develop more potent and less side effects having antitubercular activity. The reaction of 2,5-dimethoxytetrahydro furan with 4-aminobenzoate (II) in presence of ethanol, which yields ethyl 4-pyrrol-1-yl benzoate (III). This ethyl-4-pyrrol-1-yl benzoate (III) on reaction with hydrazine hydrate produced 4-pyrrol-1-yl benzoic acid hydrazide (IV). This carbohydrazide on treatment with different substituted benzoyl chlorides gave intermediates (Va-g), which on cyclisation with P2O5 in the presence of DMF yielded of 2-aryl-5-[4-(1Hpyrrol-1-yl)phenyl]-1,3,4-oxadiazoles VI(a-g). Structure of newly synthesized pyrrole derivatives were confirmed on the basis of physicochemical and spectral data (IR, 1H-NMR, 13C-NMR and Mass spectra). All the synthesized compounds were screened for their antitubercular activity using Microplate Alamar Blue Assay (MABA) method. Compounds showed anti-tubercular activity at MIC values between 1.6 to 12.5 µg/ml, compounds VIb,VIc and VId showed highest activity of 1.6 µg/ml. Selected compounds were evaluated for anti-bacterial activity against gram positive (S. aureus) and gram negative (E. coli). Compounds showed moderate activity. Physicochemical properties of the selected compounds satisfieds with the Lipinski’s rule of 5.

New series of pyrrolylpyranopyrazole were synthesized by reacting with (one pot synthesis) ethyl acetoacetate in aqueous ethanol (1), hydrazine hydrate (2), substituted aldehydes (3a-g), malononitrile (4) and triethylamine’s base stirring for 5hr the solid precipitate was obtained, it has been filtered and washed with cold water to give 6-amino-3-methyl-4-substituted phenyl-1,3a,4,7a-tetrahydropyrano [2,3-c] pyrazole-5-carbonitrile (5a-g). Further it is reacted with 4- pyrrol-1-yl benzoic acid (6) with substituted pyranopyrazoline presence of HBTU and DIEA which resulting in formation of substituted N-5-cyano-3-methyl-4-substituted phenyl 1,3a,47a-tetrahydropyrano [2,3-c] pyrazol-6-yl)-4-(1H-pyrrol-1-yl) benzamides (7a-g) was obtained. All newly synthesized compounds were confirmed by TLC and melting point. The structure of the all newly synthesized compounds were confirmed by spectral study such as IR, 1H NMR, 13C NMR and Mass spectroscopy. The newly synthesized compounds were screened for their antibacterial and antitubercular activities. Compounds exhibited antitubercular activity in the range of 1.6 to 25 µg/ml (MIC). Compounds showed antibacterial activity in the range of 0.8 to 100 µg/ml (MIC). It was indeed very much encouraging to note that most of the compounds have shown better and significant antibacterial and antitubercular activities.

The various novel nitrogen containing heterocyclic compounds were synthesized and are screened for antibacterial and antitubercular activities, purity of newly synthesized compounds confirmed by using TLC and structures for the same compounds were confirmed by using IR, NMR, 13C and Mass spectrum. Pyrrole ring was constructed by reacting benzocaine with 2, 5-dimethoxytetrahydrofuran in presence of glacial acetic acid to obtain ethyl 4-pyrrol-1-ylbenzoate (2) in good yield. Conversion of ethyl 4-pyrrol-1-ylbenzoate (2) into 4-pyrrol-1-yl-benzoic acid hydrazide (3), which was achieved by refluxing ethyl 4-pyrrol-1-ylbenzoate (2) with hydrazine hydrate in ethanol. Then this 4-pyrrol-1-yl-benzoic acid hydrazide (3) treated with appropriate benzaldehyde in presence of TCCA and ethanol to yield compound substituted 2-(4-(1H-pyrrol-1-yl)phenyl)-5-phenyl-1,3,4-oxadiazole 04(a-f).Structures of newly synthesized compounds were confirmed on the basis of physico-chemical and spectral data (IR, 1H &13C-NMR, Mass spectra). All the synthesized compounds were screened for anti-tubercular activity using Microplate Almar Blue Assay (MABA) method. Compounds showed anti-tubercular activity at MIC values between 50 to 3.12 µg/ml when compared with standard drugs Pyrazinamide (3.125 µg/ml) and Streptomycin (6.25 µg/ml).Newly synthesised compounds were also screened for antibacterial activity using broth micro dilution assay method. Compounds showed antibacterial activity at MIC values between 25 to 0.8 µg/ml when compared with standard drugs Ciprofloxacin and Norfloxacin.

The antibacterial target, enoyl-acyl carrier protein (ACP) reductase, is a homotetrameric enzyme that catalyzes the last reductive step of fatty acid biosynthesis. In the present paper, Surflex docking has been carried out on a series (10 compounds) of enoyl ACP reductase inhibitors, using the SYBYL-X 2.0 package (Tripos Inc., St. Louis, USA). Surflex-docking studies revealed that the carbonyl group and pyrazole ring were significant for binding to the receptor, and it is also found that the pattern of binding of tested compounds is same as that of the 4TZK ligand, this in turn helped in understanding of specific activity of compounds.

In present work, Surflex docking has been carried out on a series (23 compounds bearing N’-arylsubstituted pyrrole heterocyclic molecules) of M. tuberculosis inhibitors. SYBYL-X 2.0 package (Tripos Inc., St. Louis, USA) was used for the study. Surflex-docking shown that the peptide connection between the aryl substitution and pyrroly moiety was significant to exhibit receptor and molecular interactions, and it was also found that the pattern of binding of established compounds is same as that of the ligand 1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide, which gives an idea in understanding the specific activity of compounds towards the receptor.

Novel series of pyrrole derivatives were synthesized with an approach to reduce the growing anti-tubercular resistance and to develop more potent and less side effect anti-tubercular agents. Herein, we synthesized a series of substituted 2-phenoxybenzamide derivatives (3a-j) by reacting different phenoxy acetic acids with 4-(-1H-pyrrol-1-yl)benzoate (2) and a series of pyrrolyl benzamides (6a-c) were synthesized by reacting 4-(1H-pyrrol-1-yl)benzoic acid with different hydrazides 2, (5a-b) using HBTU as a coupling agent, DIEA as a catalyst and DMF as a solvent. Structures of all the newly synthesized compounds were confirmed by spectral analysis viz., IR, 1H NMR, 13C NMR and Mass. Further they were tested for their anti-tubercular and antibacterial activities and compounds showed moderate to good activity.