DESIGN, SYNTHESIS, AND EVALUATION OF NEW DERIVATIVE OF 1,2,4-TRIAZOLES FOR ANTIMICROBIAL AND ANTI-INFLAMMATORY ACTIVITY

Objective: The object of the study is to design, synthesize and biological evaluation of isoniazid derived 1,2,4-triazoles compounds.Methods: Isoniazid based 1,2,4-triazoles derivatives have been synthesized by reaction of Isoniazid with carbon disulfide in basic medium (KOH) to form Potassium dithiocarbazinate salt and reaction with hydrazine hydrate converted into 4-amino-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-thiol. These compounds were reacted with seven different benzaldehyde to form 4-[(substituted phenyl)-methylene]-amino-5-(pyridine-4-yl)-4H-1,2,4-triazol-3-thiol (4). The final compounds were synthesized by reaction with four different acetanilide to form 4-[substituted phenyl)-methylene]-amino-3-(N-substitutedcarboxamidomethylthio)-5-(pyridine-4-yl)-4H-1,2,4-triazoles derivatives. All these compounds were characterized by IR, 1H-NMR, [13]C-NMR and elemental analysis. The antimicrobial activity was determined by the cup plate method. Acute anti-inflammatory activity determined by using carrageenan-induced rat paw edema model.Results: Series PJ-A4, PJ-A7 and PJ-A13 showed more than 90% of the zone of inhibition against both Gram positive and Gram negative organisms. The antifungal study suggested that among synthesized compounds series PJ-A4, A7, A9, A11 and A13 showed more than 90% of zone of inhibition, A2, A10 and A12 shows more than 80% of the zone of inhibition. Anti-inflammatory study data indicate that compounds PJ-A4, PJ-A8, PJ-A9 and PJ-A13 produced 70 to 76% of paw edema inhibition compare to standard drug Ibuprofen which showed 83.3% after 5 h. Conclusion: Results suggested that the isoniazid based 1,2,4-triazole derivatives have significant antibacterial, antifungal and anti-inflammatory activity

Synthesis, molecular docking, antiproliferative and radical scavenging activities of vanillin derived 1,3,5-trisubstituted 2-pyrazolines

Observing the good anticancer potential of 2-pyrazoline scaffold, a panel of 1,3,5- trisubstituted 2- pyrazolinesnamely, 5-(4-hydroxy-3-methoxyphenyl)-3-(4-substitutedphenyl)4,5-dihydro-1H-pyrazol-1 yl)(phenyl)methanones 2a-j and (5-(4-hydroxy-3-methoxyphenyl)-3-(4-substituted phenyl)4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones 3a-j have been synthesized from the chalcone intermediates derived from the reaction between vanillin and substituted acetophenones, by condensing with benzhydrazide and isonicotinic acid hydrazide, respectively. The synthesized compounds have been characterized by spectral studies and screened for in vitro antiproliferative activity against human non small cell lung cancer cell line A549 by MTT assay and antioxidant activity by DPPH radical scavenging assay. The compound 2i has exhibited good antiproliferative activity followed by 2g and 2a. Compounds of both series 2a-j and 3a-j exhibited good radical scavenging activity. Molecular docking studies of 2h and 2j has revealed the good interaction with 3LCT (Crystal structure of anaplastic lymphoma kinase catalytic domain) receptor via hydrogen bonds, electrostatic and hydrophobic interactions. The drug-likeness properties of the compounds were also satisfactory leaving a good scope for further work

Synthesis, molecular docking, antiproliferative and radical scavenging activities of vanillin derived 1,3,5-trisubstituted 2-pyrazolines

732-743Observing the good anticancer potential of 2-pyrazoline scaffold, a panel of 1,3,5- trisubstituted 2- pyrazolines namely, 5-(4-hydroxy-3-methoxyphenyl)-3-(4-substitutedphenyl)4,5-dihydro-1H-pyrazol-1 yl)(phenyl)methanones 2a-j and (5-(4-hydroxy-3-methoxyphenyl)-3-(4-substituted phenyl)4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones 3a-j have been synthesized from the chalcone intermediates derived from the reaction between vanillin and substituted acetophenones, by condensing with benzhydrazide and isonicotinic acid hydrazide, respectively. The synthesized compounds have been characterized by spectral studies and screened for in vitro antiproliferative activity against human non small cell lung cancer cell line A549 by MTT assay and antioxidant activity by DPPH radical scavenging assay. The compound 2i has exhibited good antiproliferative activity followed by 2g and 2a. Compounds of both series 2a-j and 3a-j exhibited good radical scavenging activity. Molecular docking studies of 2h and 2j has revealed the good interaction with 3LCT (Crystal structure of anaplastic lymphoma kinase catalytic domain) receptor via hydrogen bonds, electrostatic and hydrophobic interactions. The drug-likeness properties of the compounds were also satisfactory leaving a good scope for further work