Synthesis and cytotoxic effects on HeLa cervical cancer cells of (E)-2-aroyl-4-(4-fluorobenzylidene)-5-oxopyrrolidine

Abstract

Seven ( E)-2-aroyl-4-(4-fluorobenzylidene)-5-oxopyrrolidines were synthesized via a tandem Ugi 4CC/SN cyclization sequence starting from a Baylis-Hillman-derived acid, primary amines, arylglyoxals, and isocyanides in one pot. In addition, the cytotoxicity of these compounds on the cervical cancer cell line HeLa was studied by MTT assay. The results showed that most of the compounds could inhibit the proliferation of HeLa cells significantly.

Synthesis and Anticancer Activity of Rhopaladins’ Analog RPDPD Against the HeLa Human Cervical Cancer Cell Line

“…Rhopaladin B has inhibitory activity against CDK4 and c-erbB-2 kinases (IC 50 of 12.5 and 7.4 μg/ml, respectively) ( Hiroyasu et al, 1998 ; Zhu et al, 2019 .). We have previously synthesized rhopaladins’ analogs 2-aroyl-4-arylidene-5-oxopyrrolidine derivatives (see Scheme 1 ) via a tandem Ugi 4CC/S N cyclization and studied their cytotoxicity to HeLa cells ( Wang et al, 2020 ). According to the existing structure–activity relationship analysis ( Wang et al, 2020 ), in order to obtain a compound with good anti-cervical cancer activity (fluorine-containing) and low hepatotoxicity (bromine-containing), a new rhopaladins’ analog( E )-2-(4-bromobenzoyl)- N -( tert -butyl)-4-(4-fluorobenzylidene) -5-oxo-1-propylpyrrolidine-2-carboxamide (RPDPD for short) of 2-aroyl-4-arylidene-5-oxopyrrolidine derivative was synthesized by a similar method (see Scheme 2 ).…”

“…We have previously synthesized rhopaladins’ analogs 2-aroyl-4-arylidene-5-oxopyrrolidine derivatives (see Scheme 1 ) via a tandem Ugi 4CC/S N cyclization and studied their cytotoxicity to HeLa cells ( Wang et al, 2020 ). According to the existing structure–activity relationship analysis ( Wang et al, 2020 ), in order to obtain a compound with good anti-cervical cancer activity (fluorine-containing) and low hepatotoxicity (bromine-containing), a new rhopaladins’ analog( E )-2-(4-bromobenzoyl)- N -( tert -butyl)-4-(4-fluorobenzylidene) -5-oxo-1-propylpyrrolidine-2-carboxamide (RPDPD for short) of 2-aroyl-4-arylidene-5-oxopyrrolidine derivative was synthesized by a similar method (see Scheme 2 ). We investigated the cytotoxic and apoptotic effects of compound RPDPD on HeLa cell lines and preliminarily explored the relationship between RPDPD and TIMP3/MMP3 signaling axis.…”

Green synthesis, structure optimization and biological evalution of Rhopaladins’ analog 2–styryl–5-oxopyrrolidine-2- carboxamide RPDPRH on CaSki cells

“…Among them, alkaloid Rhopaladins A-D isolated from marine natural products has obvious anti-tumor activity ( Sato et al, 1998 ). Hence, Rhopaladins’ analogs ( E )-2-aroyl-4-arylidene-5-oxopyrrolidine (RPDP serial chemicals) have been synthesized by one-pot method using Ugi condensation and intramolecular S N Cyclization ( Zeng et al, 2013 ; Wang et al, 2020b ), and ( E )- N -( tert -butyl)-2-(4-chlorobenzoyl)-4-(4-fluorobenzylidene)-1-isopropyl-5-oxopyrrolidine-2-carboxamide (RPDPB for short) effects on proliferation, apoptosis and E6/E7 mRNA of cervical cancer CaSki cells were studied ( Zhu et al, 2020 ). Further, in order to obtain compounds with better apoptosis inducing activity of tumor cells, analogs of Rhopaladins (2 E ,4 E )-4-arylidene-2-styryl-5-oxopyrrolidine (RPDPR serial chemicals) were synthesized after structural optimization ( Kong et al, 2021 ).…”