Rhopaladins' analogue (E)-2-aroyl-4-(4-fluorobenzylidene)-5-oxopyrrolidines inhibit proliferation, promote apoptosis and down-regulation of E6/E7 mRNA in cervical cancer

Zhu, Xiu-Lian; Tian, Xiao-Qiong; Xu, Huanhuan; Wang, Hongmei; Chen, Qinhua; Zeng, Xiao‐Hua

doi:10.1016/j.bmcl.2020.127554

Cited by 9 publications

(10 citation statements)

References 13 publications

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“…Cell viability was measured by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, MultiSciences, China) assay. The specific experimental steps referred to our previous research ( Zhu et al, 2020 ). For each cell line, cells were digested and seeded in 96-well plates at a density of 1 × 10 3 cells/well.…”

Section: Methodsmentioning

confidence: 99%

“…Alkaloids such as rhopaladins A-D have momentous cytotoxicity to human tumor cells ( Hiroyasu et al, 1998 ). We have previously synthesized rhopaladins’ analog ( E )-2-aroyl-4-arylidene-5-oxopyrrolidine (RPDP serial chemicals, see Scheme 1 ) from Baylis–Hillman acid (2-bromomethyl-3- p -fluorobenzyl-2-propenoic acid), primary amines, arylglyoxal, and isocyanide via a one-pot approach which is based on Ugi condensation and intramolecular S N cyclization ( Zhu et al, 2020 ). Moreover, the rhopaladins’ analogs ( E )-2-aroyl-4-arylidene-5-oxopyrrolidine inhibited CaSki human cervicocarcinoma cell proliferation, induced cell apoptosis, and downregulated the E6/E7 mRNA expression ( Zeng et al, 2013 ; Wang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Rhopaladins’ Analog 4-Arylidene-5-Oxopyrrolidine Derivatives

Zhu

Kong

Chen³

et al. 2022

Front. Chem.

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Marine alkaloids have novel structures and antitumor activities. Therefore, we synthesized rhopaladins’ analogs from marine alkaloids rhopaladins A-D and modified their structures to synthesize 4-benzylidene-5-pyrrolidone derivatives. Among the compounds, (2E, 4E)-4-(4-chlorobenzylidene)-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) has high efficiency and less hepatotoxicity, with IC50 values of 4.66, 6.42, 17.66, 15.2, 12.36, 22.4, and 243.2 μM in vitro anti-proliferative activity testing against cervical cancer C-33A, CaSki, SiHa, and HeLa cells, human hepatocarcinoma HepG2 and 7402 cells, and human normal liver LO2 cells, respectively. In particular, RPDPRH has similar activity to cisplatin on human hepatocarcinoma cells, and cisplatin served as a positive control in our study. Next, the apoptosis of HepG2 and 7402 cells induced by RPDPRH at different concentrations was detected by Annexin V/PI flow cytometry. Moreover, the expression of apoptotic proteins was detected by Western blot analysis. Finally, the results showed that RPDPRH could induce apoptosis of hepatocarcinoma cells by regulating Bax and Bcl-2 expressions. In summary, our results indicate that RPDPRH has the potential to serve as an antitumor agent and plays a significant role in future studies.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Rhopaladins’ Analog 4-Arylidene-5-Oxopyrrolidine Derivatives

Zhu

Kong

Chen³

et al. 2022

Front. Chem.

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“…normal hepatocyte cell lines (LO2). We treated cells with different concentrations of compounds 6 and determined the IC 50 values of each compound, with cisplatin and RPDPB (prior synthetic compound 11…”

Section: In Vitro Cytotoxicity Assaymentioning

confidence: 99%

“…MTT assays were carried out to determine the growth inhibitory effects of compounds 6 toward: five cell lines (C-33A, CaSki, SiHa, HeLa, and HepG2) and one normal hepatocyte cell lines (LO2). We treated cells with different concentrations of compounds 6 and determined the IC 50 values of each compound, with cisplatin and RPDPB (prior synthetic compound 11 (2E)-N-(tert-butyl)-2-(4-chlorobenzoyl)-4-(4-fluorobenzylidene)-1-isopropyl-5oxopyrrolidine-2-carbox-amide) as the reference control. The results in Table 1 show that compounds 6a-f have low cytotoxicity toward the cancer cells.…”

Section: In Vitro Cytotoxicity Assaymentioning

confidence: 99%

“…10 We have previously synthesized (E)-2-aroyl-4-arylidene-5oxopyrrolidinerhopaladin analogues from a Baylis-Hillman acid (2-bromomethyl-3-p-fluorobenzyl-2-propenoic acid), primary amines, arylglyoxals and isocyanides via a one-pot approach based on Ugi condensation and intramolecular S N cyclization. 11 These rhopaladin analogues inhibit the proliferation of the CaSki cervical cancer cell line, induce cell apoptosis, and down-regulate E6/E7 mRNA expression. 12,13 In addition, they have high selectivity toward cervical cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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One-pot synthesis and biological evaluation of (2E,4E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives

Kong

Zhu

Chen³

et al. 2021

Journal of Chemical Research

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Many marine alkaloids possess interesting structures and antitumor activities. Thus, we have synthesized (2 E,4 E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives of the marine alkaloids, rhopaladins A–D. The cytotoxicities of these derivatives against C-33A, CaSki, SiHa, HeLa, HepG2, and LO2 cells are evaluated by MTT assays. The results show that (2 E,4 E)-2-(4-chlorostyryl)-4-benzylidene- N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide significantly inhibits cancer cell proliferation, with IC50 values against C-33A, CaSki, SiHa, HeLa, and HepG2 cells of 5.56, 9.15, 12.5, 21.4, and 14.5 μM, respectively, and an IC50 value of 86.77 μM against the normal LO2 cell line.

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Deselenylative Acylation and Nitration of Monoselenides

Xuan,

Chen,

Liu

et al. 2024

Org. Lett.

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A deselenylative protocol that enables the construction of the C−C and C−N bonds has been disclosed. By using acyl chloride/AgOTf as an efficient acylation reagent, diarylselenides smoothly undergo deselenylative acylation to produce a series of aroyl compounds. In addition, deselenylative nitration can be enabled by a mild nitration reagent consisting of TsCl and AgNO 3 , furnishing a diverse array of nitroaromatic compounds.

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Rhopaladins' analogue (E)-2-aroyl-4-(4-fluorobenzylidene)-5-oxopyrrolidines inhibit proliferation, promote apoptosis and down-regulation of E6/E7 mRNA in cervical cancer

Cited by 9 publications

References 13 publications

Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Rhopaladins’ Analog 4-Arylidene-5-Oxopyrrolidine Derivatives

Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Rhopaladins’ Analog 4-Arylidene-5-Oxopyrrolidine Derivatives

One-pot synthesis and biological evaluation of (2E,4E)-4-arylidene-2-styryl-5-oxopyrrolidine derivatives

Deselenylative Acylation and Nitration of Monoselenides

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