DESIGN, SYNTHESIS, MOLECULAR DOCKING, AND BIOLOGICAL EVALUATION OF PYRAZOLE 1-CARBOTHIAMIDE INCORPORATED ISOXAZOLE DERIVATIVES
Journal Title: Asian Journal of Pharamceutical and Clinical Research - Year 2019, Vol 12, Issue 5
Abstract
Objectives: Novel isoxazole incorporated pyrazole carbothiamide 5 (a-r) was designed and synthesized, docked and evaluated for anticancer activity Michigan Cancer Foundation-7 (MCF-7), and breast cancer cell lines. Materials and Methods: Designed compounds were synthesized by the condensation of 1-(5-methyl-3-(4-nitrophenyl) isoxazole-4-yl) -3-(substitutedphenyl) prop-2-en-1-one (4) with thiosemicarbazides and substituted thiosemicarbazides to give the target molecules 5 (a-r). To predict the affinity and activity of the ligand molecule, the docking program Accelrys Discovery Studio 2.1 was employed to generate different bioactive binding poses of designing molecules at the active site of human Dihydrofolate Reductase (DHFR) (PDB ID: 1KMS). All the synthesized compounds were characterized based on the spectral and elemental analysis data. Antiproliferative activity was performed against MCF-7 breast cancer cell lines. Results: All the synthesized compounds showed the characteristic peaks in Fourier-transform infrared,1H C13NMR, and mass spectral analysis. During docking, all the synthesized compounds 5 (a-r) exhibited higher fitness scores with minimum three bonding interaction with the active site human DHFR (PDB ID: 1KMS). In the MTT assay based on MCF-7 breast cancer cell lines, most of the compounds exhibited significant activity. In the antiproliferative assay against MCF-7 cell lines, most of the compounds exhibited potent activity with IC50 values in micromolar concentrations. Compounds 5a, 5b, 5f, 5h, and 5k have exhibited significant anticancer activity. Conclusions: The derivatives were synthesized in quantitative yields. New derivatives possess the antiproliferative activity and antitubercular activity.
Authors and Affiliations
RADHIKA TUMMA , HARINADHA BABU VAMARAJU
Keywords
Related Articles
- EP ID EP604750
- DOI -
- Views 115
- Downloads 0
AN ETHNOBOTANICAL STUDY OF WILD MEDICINAL PLANTS USED BY MIGRATORY SHEPHERDS – A TRIBAL COMMUNITY OF WESTERN HIMALAYAS
Objectives: Migratory shepherds of Kinnaur, Shimla, and Sirmaur districts in Himachal Pradesh of the western Himalayas have rich traditional knowledge of medicinal plants and its uses, in this respect; an ethnobotanical...
COLOR INTENSITY AND ANTIOXIDATIVE CAPACITY OF FOUR NATURAL MONOFLORAL HONEY FROM MALDA, INDIA
Objective: The objective of the study was to explore the color intensity and antioxidative capacity of mango honey available from local niches, in and around Malda, West Bengal, India. Methods: Four mango honey samples:...
EVALUAION OF ANTI-INFLAMMATORY AND ANTI PYRETIC ACTIVITY OF ETHANOLIC LEAVES EXTRACT OF Myxopyrum smilacifolium (Wall.) Blume
ABSTRACTObjective: The aim of this study was to evaluate the anti-inflammatory and antipyretic activity of ethanolic extract of Myxopyrum smilacifolium(EEMS) leaves in experimental animals.Methods: Plant material was col...
A STUDY ON UTILIZATION OF ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS IN PATIENTS WITH CARDIOVASCULAR DISEASES
Objectives: The objective of this study was to assess the prescribing pattern, most common indication, and adverse effects associated with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blocker...
FORMULATION AND EVALUATION OF CEFIXIME TRIHYDRATE TOPICAL GEL FOR WOUND INFECTIONS
Objective: The objective of this research work was to formulate and evaluate topical gel loaded with cefixime trihydrate, a third-generation cephalosporin antibiotic for the treatment of bacterial wound infections.Method...