Synthesis, cytotoxic study and docking based multidrug resistance modulator potential analysis of 2-(9-oxoacridin-10(9H)-yl)-N-phenyl acetamides.
The present study describes the synthesis of fifteen 2-(9-oxoacridin-10(9H)-yl)-N-phenyl acetamide derivatives (13a-o) through condensation of 2-chloro-N-phenyl acetamides (12a-o) with acridone molecule (10). All the synthesized compounds were screened for their anti-cancer activity against three diverse cell lines including breast (MCF-7), cervical (HeLa) and lung adenocarcinoma (A-549) employing standard MTT assay. Among synthesized molecules, 13k and 13l showed good cytotoxicity activity against considered three cancer cell lines. Additionally, in silico studies of multidrug resistance modulator (MDR) effects of these compounds was performed by docking simulation in the ATP binding site of P-gp. The results of docking simulation displayed important interactions of these molecules in the active site of this protein and predicted their MDR modulator behavior.
Pharmaceutical Chemistry Division, Shivalik College of Pharmacy, Nangal, Punjab 140126, India; Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
Rajesh
R
Kumar
Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
Maninder
M
Kaur
Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
Malkeet Singh
MS
Bahia
Molecular Modeling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India. Electronic address: omsilakari@rediffmail.com.
Om
O
Silakari
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism; D000081:Acetamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011487:Protein Conformation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000081:Acetamides; D000970:Antineoplastic Agents; D000255:Adenosine Triphosphate
Acridone derivatives; Cytotoxicity; Docking analysis; MTT assay; Multidrug resistance