SYNTHESIS OF NOVEL CYCLOHEXANONE DERIVATIVES AS BCR-ABL T1351 INHIBITORS
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2015, Vol 7, Issue 12
Abstract
Objective: Several 3(rd) generation inhibitors are being developed for the treatment of patients with Chronic myelogenous leukemia (CML). The present work mainly aims to discover novel small molecular inhibitors against important molecular target T3151 ABL mutant involved in leukemia.Methods: Docking study was carried out and the binding affinity of the proteins with the phenothiazine compounds 3a-h and 7a-c was measured. The docking scores of the N-acylated compounds 7a-c are higher than 3a-h. The drug likeliness of these compounds was tested by the Lipinski’s rule of five. The phenothiazine compounds with good docking scores and 7a-c were synthesized and screened by in-vitro methods for inducing antiproliferative effect by trypan blue and MTT assay and induction of apoptosis in K562 cells.Results: All the N-acylated compounds and, in particular, 7c with a chloro substituent in the para position of the phenyl ring appeared to be most potent molecule with an IC50 value of 32.44 and 24.01(µg/ml) by trypan blue and MTT assay respectively. Further, a dose-dependent increase in LDH release was observed, confirming the antiproliferative potential of the compounds.Conclusion: The compounds 7a-c was tested for antiproliferative effect against K562 cell lines by MTT assay LDH assay and Trypan blue assay. All the compounds 7a-h behaves as 3(rd) generation inhibitors for the treatment of patients with Chronic myelogenous leukemia (CML). These can act as a template for the further development and optimization studies.Â
Authors and Affiliations
Sulaiman Ali Muhammad, Subash Suganya, Subban Ravi, Senniappan Venkatachalapathi
Keywords
Related Articles
- EP ID EP578055
- DOI -
- Views 70
- Downloads 0
INHIBITION OF TUMOUR NECROSIS FACTOR (TNF) ACTIVITY BY A NEW ERGOSTANE STEROID FROM CLEOME DROSERIFOLIA
Objective: To isolate steroidal compound from Cleome droserifolia and explore its activity against tumour necrosis factor (TNF) using molecular docking studies.Methods: Extraction of the plant material was carried using...
THE BLISS YOGA INCULCATES DURING THE DIFFERENT STAGES OF PREGNANCY
Yoga is the Sanskrit word for ‘union’, and through the practice of yoga the mind, body and breath are united. During pregnancy one lives and breathes with her baby and the baby becomes aware of her thoughts, movement...
EVALUATION AND PHARMACIST’S INTERVENTION FOR IMPROVING ADHERENCE AMONG RENAL FAILURE PATIENTS
Objective: Management of renal disease may include pharmacotherapy, dialysis, life style modifications, organ transplants and immunosuppressive therapy. Lack of adherence and proper perception towards prescribed renal fa...
DESIGN, IN-SILICO DOCKING AND PREDICTIVE ADME PROPERTIES OF NOVEL PYRAZOLINE DERIVATIVES WITH SELECTIVE HUMAN MAO INHIBITORY ACTIVITY
Objectives: Curcumin, a known hMAO-A (human Monoamine oxidase-A) inhibitor from Curcuma longa has never been recognized for this property due to its poor permeability and extensive metabolism. Thus, the main objective of...
SCREENING OF CELLULOLYTIC BACTERIA FOR PRODUCING CELLULASE UNDER SOLID STATE FERMENTATION USING WATER HYACINTH AS A SUBSTRATE
Objective: The infestation of water hyacinth in the aquatic system produces serious environmental problems. In our study, we have used the water hyacinth as a substrate for the production of cellulase enzyme from bacteri...