Synthesis of (Z)-1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(phenylamino)prop-2-en-1-one derivatives as potential anticancer and apoptosis inducing agents.
A series of (Z)-1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(phenylamino)prop-2-en-1-one derivatives were synthesized and characterized by (1)H and (13)C NMR, ESI-MS and HRMS. All the synthesized compounds were evaluated for their anticancer activity against HT-29, PC-3, A549 and U87MG human tumor cell lines. Most of the synthesized compounds displayed potent growth inhibition selectively of A549 cancer cells and did not show significant toxicity to the non-cancerous HaCaT cells. Some of the representative compounds, particularly, 16, 22 and 28 exhibited potent growth inhibition with IC50 values in the range of 1.25-3.98 μM, which are comparable or even better than the standard chemotherapeutic drug 5-fluorouracil. Preliminary mechanistic studies revealed that these compounds could effectively inhibit the migration ability of A549 cells. Flow-cytometry analysis revealed that the compounds treatment led to G2/M cell cycle arrest. Moreover, the compounds induced apoptosis in A549 cells through depolarization of mitochondrial membrane potential (DΨm) and increased reactive oxygen species (ROS) production, suggesting their potential to act as promising lead compounds for the development of cancer chemotherapeutics.
Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Victoria 3000, Australia.
T
T
Srinivasa Reddy
Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
V
V
Ganga Reddy
Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Victoria 3000, Australia.
Hitesh
H
Kulhari
Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Victoria 3000, Australia; Centre for Advanced Materials and Industrial Chemistry, School of Science, RMIT University, Melbourne, Victoria 3000, Australia.
Ravi
R
Shukla
Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India. Electronic address: ahmedkamal@iict.res.in.
Ahmed
A
Kamal
Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Victoria 3000, Australia. Electronic address: vipul.bansal@rmit.edu.au.
Vipul
V
Bansal
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011720:Pyrazoles; D017382:Reactive Oxygen Species
Anti-cancer activity; Apoptosis; Cell cycle; Pyrazole