Synthesis of Triphenylethylene‐Naphthalimide Conjugates as topoisomerase‐IIα inhibitor and HSA binder

Abstract

A series of triphenylethylene‐naphthalimide (TPE‐naph) conjugates was synthesized by a molecular hybridization technique, and their anticancer activity was evaluated in vitro on 60 human cancer cell lines through their cytotoxicity. The ratios of E and Z isomers were determined on the basis of HPLC methodology and NMR spectroscopy. The structure‐activity relationship for anticancer activity was deduced on the basis of the nature and bulkiness of the amine attached to the C‐4 position of the naphthalene ring. Experimental and molecular modeling studies of the most active TPE‐naph conjugate bearing a morpholinyl group showed that it was able to inhibit topoisomerase‐II (TOPO‐II) as a possible intracellular target. Moreover, the transportation behavior of TPE‐naph conjugate towards human serum albumin (HSA) indicated efficient binding affinity. The steady‐state and time‐dependent fluorescent results suggested that this conjugate quenched HSA significantly through static as well as dynamic quenching. Thus, this report discloses the scope of triphenylethylene‐naphthalimide (TPE‐naph) conjugates as efficient anticancer agents.

Investigating the Serum Albumin Binding Behavior of Naphthalimide Based Fluorophore Conjugates: Spectroscopic and Molecular Docking Approach

“…Compound 7 was synthesized by reduction of 6 in THF: water (3 : 1) in the presence of sodium dithionite and ammonia at room temperature for 1 h in 70 % yield. Further reaction of 7 and 8 in ethanol in the presence of zinc acetate at reflux condition for 6 h to form 9 in 65 % yield [28] …”

“…in the presence of zinc acetate at reflux condition for 6 h to form 9 in 65 % yield. [28] Finally, the naphthalimide ring of compound 9 was substituted with various primary and secondary amines using DMF and K 2 CO 3 at 70 °C to form analogs 10-27 in the range of 65 %-75 %. The spectral data like 1 H NMR, 13 C NMR, FT-IR and HRMS were in consonance with structures of compounds 10-27 (Figures S1-S61).…”

Engineered Artesunate-Naphthalimide Hybrid Dual Drug for Synergistic Multimodal Therapy against Experimental Murine Lymphoma

“…TPE-naph conjugate bearing a morpholinyl group inhibits topoisomerase II. 18 Our objective is to develop a successful nucleus-targeting (naphthalimide moiety) drug in combination with a nononcogenic drug (ARTN: antimalarial drug) upon remodeling in a new direction of drug discovery to validate antilymphoma activity. To validate the in vivo biodistribution, the synthesized DNA-targeting novel molecule was attached with FITC (imaging agent).…”

“…Riphenylethylene-naphthalimide (TPE-naph) conjugates were synthesized by a molecular hybridization technique and evaluated for anticancer activity (cytotoxicity) against human cancer cell lines. TPE-naph conjugate bearing a morpholinyl group inhibits topoisomerase II …”