ABSTRACT
A series of biologically active novel Mannich bases containing with a 1H-1,2,4-triazole-5-one ring were developed to evaluate the cytotoxic activity. For this purpose, the synthesized Schiff Bases (S1-5) were reacted with formaldehyde and morpholine, which is a secondary amine to yield novel N-Mannich bases (M1-5) via the Mannich reaction. The structures of the compounds (M1-5) were determined structurally employing 1H/13C-NMR, IR and elemental analysis. In this study, we evaluated the cytotoxic potential of the compounds (M1-5) on the human hypopharyngeal carcinoma FaDu cells. We found that the compound (M3) possesses a significant anticancer feature against FaDu cells that might be evaluated with further in vitro and in vivo studies to understand its anticancer potential better. Lastly, comparisons were made using molecular docking calculations to find the theoretical activities of the compounds (M1-5). The docking score parameter of the compound (M3) against the 2DO4 protein is -5.67, the docking score parameter against the 5JPZ protein is -5.72, and finally, the docking score parameter against the 2H80 protein is -5.50. Molecular dynamic calculations are made for 0-100 ns. The ADME/T calculations were performed to find the drug potential of the compounds (M1-5). The results suggest that our drug candidate compound exhibits strong potential for co-administration with the antigen structures, owing to the low rate of interactions that decreased over time.Communicated by Ramaswamy H. Sarma.
ABSTRACT
3-Alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2a-g reacted with 4-diethylaminobenzaldehyde to afford the corresponding 3-alkyl(aryl)-4-(4-diethyl-aminobenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3a-g. The acetylation reactions of compounds 3a-e were investigated and compounds 4a-e were thus obtained. The new compounds were characterized using IR, (1)H-NMR, (13)C-NMR, UV and MS spectral data. In addition, the newly synthesized compounds 3a-g were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as isopropyl alcohol, tert-butyl alcohol, acetone and N,N-dimethylformamide (DMF), and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Moreover, 3 and 4 type compounds were also screened for their antioxidant activities.
Subject(s)
Antioxidants/chemistry , Antioxidants/chemical synthesis , Triazoles/chemistry , Triazoles/chemical synthesis , Chelating Agents/pharmacology , Ferricyanides/chemistry , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Metals , Oxidation-Reduction/drug effects , Potentiometry , Solvents , Titrimetry , alpha-Tocopherol/pharmacologyABSTRACT
Six novel 3-alkyl(aryl)-4-(p-nitrobenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5- ones (2a-f) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H- 1,2,4-triazol-5-ones (1a-f) with p-nitrobenzoyl chloride and characterized by elemental analyses and IR, (1)H-NMR, (13)C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as acetone, isopropyl alcohol, tert-butyl alcohol and N,N-dimethylformamide, and the half-neutralization potential values and the corresponding pK(a) values were determined for all cases. Thus, the effects of solvents and molecular structure upon acidity were investigated. In addition, isotropic (1)H and (13)C nuclear magnetic shielding constants of compounds 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound has been optimized using the 6-311G basis set. Theoretical values were compared to the experimental data. Furthermore, these new compounds and five recently reported 3-alkyl-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3a-c,e,f) were screened for their antioxidant activities.
ABSTRACT
Five novel 3-alkyl-4-phenylacetylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) were synthesized by the reactions of 3-alkyl-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with phenylacetyl chloride and characterized by elemental analyses and IR, 1HNMR, 13C-NMR and UV spectral data. The newly synthesized compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide, and the half-neutralization potential values and the corresponding pKa values were determined for all cases. In addition, these new compounds and five recently reported 3-alkyl-4-(pmethoxybenzoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3) were screened for their antioxidant activities.
Subject(s)
Antioxidants/chemistry , Free Radical Scavengers/chemistry , Triazoles/chemistry , Antioxidants/chemical synthesis , Biphenyl Compounds/chemistry , Ferricyanides/chemistry , Free Radical Scavengers/chemical synthesis , Hydrazines/chemistry , Molecular Structure , Oxidation-Reduction , Picrates , Potentiometry , Spectrum Analysis , Triazoles/chemical synthesisABSTRACT
Four novel 3-alkyl(aryl)-4-(4-methoxycarbonylbenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with methyl 4-formylbenzoate and characterized by elemental analyses and IR, 1H NMR, 13C NMR and UV spectral data. In addition, isotropic 1H and 13C nuclear magnetic shielding constants of 2 were obtained by the gauge-including-atomic-orbital (GIAO) method at the B3LYP density functional level. The geometry of each compound was optimized using the 6-311G basis set.
Subject(s)
Magnetic Resonance Spectroscopy/methods , Models, Chemical , Models, Molecular , Triazoles/analysis , Triazoles/chemistry , Algorithms , Carbon Isotopes , Molecular Conformation , ProtonsABSTRACT
The synthesis of 3-alkyl(aryl)-4-(3-ethoxy-4-hydroxybenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3 from the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2 with 3-ethoxy-4-hydroxybenzaldehyde is described. The acetylation and methylation reactions of the compounds 3 giving compounds of type 4 and 5, respectively, were investigated. The newly synthesized compounds were characterized using elemental analyses and IR, (1)H-NMR, (13)C-NMR and UV spectral data. In addition, to investigate the effects of solvents and molecular structure upon acidity,compounds 3 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, acetonitrile and N,N-dimethylformamide). The half-neutralization potential values and the corresponding pKa values were determined for all cases.
Subject(s)
Triazoles/chemical synthesis , 2-Propanol/chemistry , Dimethylformamide/chemistry , Hydrogen-Ion Concentration , Potentiometry , Solutions , Triazoles/chemistryABSTRACT
3-Alkyl(Aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) reacted with 2-furoyl chloride and thiophene-2-carbonyl chloride to afford the corresponding 3- alkyl(aryl)-4-(2-furoylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (3) and 3-alkyl(aryl)- 4-(2-thienylcarbonylamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4), respectively. The new compounds synthesized were characterized by using IR, 1H-NMR, 13C-NMR and UV spectral data together with elemental analysis. In addition, to investigate the effects of solvents and molecular structure upon acidity, compounds 3 and 4 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, N,N-dimethylformamide and acetonitrile). The half-neutralization potential values and the corresponding pKa values were determined for all cases.