Concise Synthesis of 1,1-Diarylvinyl Sulfones and Investigations on their Antiproliferative Activity <i>via</i> Tubulin Inhibition

Author(s):

Lavanya Reddy, Suja T. Dharmabalan*, Kanakaraju Manupati, Ragini Yeeravalli, Lakshmi D. Vijay, Kavitha Donthiboina, Vadithe Lakshma Naik and Amitava Das   Pages 1469 - 1474 ( 6 )

Abstract:

Background: Discovery of small molecules that inhibit tubulin polymerization is an attractive strategy for the development of new and improved anti-proliferative agents. <p></p> Objective: A series of novel 2-sulfonyl-1,1-diarylethenes were designed towards this end keeping in view the favorable chemical and pharmacological virtues of unsaturated sulfones. <p></p> Methods: Rapid, convenient and efficient two-step assembly of the designed molecules was achieved by the vicinal iodo-sulfonylation-Suzuki coupling sequence. <p></p> Results: As hypothesized, these compounds showed good anti-proliferative activity against different tissuespecific cancer cell lines: MCF-7, DU-145, A-549, HepG2, and HeLa. The most active compound, pnitrophenyl ring-bearing analog, exhibited an IC50 value of 0.90μM against A-549 cells. Flow cytometry studies on this derivative revealed that it arrests the cell cycle of A-549 cells at the G2/M phase. This compound exhibited molecular binding to tubulin as well as tubulin polymerization inhibition comparable to that of colchicine. <p></p> Conclusion: A new class of potent, tubulin binding anticancer agents based on 1,1,-diarylvinyl sulfone scaffold has been designed and synthesized.

Keywords:

Tubulin polymerization inhibitor, vinyl sulfone, diarylethenes, ceric ammonium nitrate, Suzuki-Miyaura coupling, antiproliferative activity.

Affiliation:

Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, Deen Dayal Upadhyay Kaushal Kendra (DDU KK), Central University of Haryana, Mahendergarh 123 029, Haryana, Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana, Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Telangana

Graphical Abstract:

Read Full-Text article