Preparation of Dearomatized p-Coumaric Acid Derivatives as DNA Damage Response Inhibitors with Potent In Vitro Antitumor Effect

被引：0

作者：

Fasi, Laura ^{[1
,4
]}

Gonda, Timea ^{[1
]}

Toth, Noemi ^{[1
]}

Vass, Mate ^{[1
]}

Gyovai, Andras ^{[5
]}

Nagy, Viktoria ^{[5
]}

Ocsovszki, Imre ^{[6
]}

Zupko, Istvan ^{[5
]}

Kusz, Norbert ^{[1
]}

Nove, Marta ^{[7
,8
]}

Spengler, Gabriella ^{[7
,8
]}

Berkecz, Robert ^{[9
]}

Wang, Hui-Chun ^{[4
]}

Chang, Fang-Rong ^{[4
]}

Hunyadi, Attila ^{[1
,2
,3
]}

机构：

[1] Univ Szeged, Inst Pharmacognosy, Eotvos Str 6, H-6720 Szeged, Hungary

[2] HUN REN SZTE Biologically Act Nat Prod Res Grp, Eotvos Str 6, H-6720 Szeged, Hungary

[3] Univ Szeged, Interdisciplinary Ctr Nat Prod, Eotvos Str 6, H-6720 Szeged, Hungary

[4] Kaohsiung Med Univ, Grad Inst Nat Prod, Shih Chuan 1st Rd 100, Kaohsiung 807, Taiwan

[5] Univ Szeged, Dept Pharmacodynam & Biopharm, Eotvos Str 6, H-6720 Szeged, Hungary

[6] Univ Szeged, Fac Med, Dept Biochem, Dom Sq 9, H-6720 Szeged, Hungary

[7] Univ Szeged, Albert Szent Gyorgy Hlth Ctr, Dept Med Microbiol, Semmelwe Str 6, H-6725 Szeged, Hungary

[8] Univ Szeged, Albert Szent Gyorgy Med Sch, Semmelwe Str 6, H-6725 Szeged, Hungary

[9] Univ Szeged, Inst Pharmaceut Anal, Somogyi Str 4, H-6720 Szeged, Hungary

来源：

CHEMMEDCHEM | 2024年 / 19卷 / 19期

关键词：

hydroxycinnamic acid derivative; alkylation; triple-negative breast cancer; multidrug resistance; DNA damage; ATR; HYDROXYCINNAMIC ACIDS; CANCER-CELLS; AGENTS; INDUCTION; ESTERS;

D O I：

10.1002/cmdc.202300675

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Our research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl-substituted derivatives and tested their in vitro antitumor potential. All new compounds bypassed ABCB1-mediated multidrug resistance and showed highly different cell line specificity compared with 1. All compounds were more potent in MDA-MB-231 than on MCF-7 cells. The n-butyl-substituted derivatives 2 and 8 modulated the cell cycle and inhibited the ATR-mediated phosphorylation of checkpoint kinase-1 in MCF-7 cells. As a significant expansion of our previous findings, our results highlight the potential antitumor value of alkyl-substituted graviquinone derivatives.

引用

页数：6

共 36 条

[21] Anti-inflammatory effects of hydroxycinnamic acid derivatives
Nagasaka, Reiko
Chotimarkorn, Chatchawan
Shafiqul, Islam Md.
Hori, Masatoshi
Ozaki, Hiroshi
Ushio, Hideki
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 358 (02) : 615 - 619
[22] Stereoconvergent Synthesis of Chiral Allylboronates from an E/Z Mixture of Allylic Aryl Ethers Using a 6-NHC-Cu(I) Catalyst
Park, Jin Kyoon
Lackey, Hershel H.
Ondrusek, Brian A.
McQuade, D. Tyler
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2011, 133 (08) : 2410 - 2413
[23] A RETROVIRUS CARRYING AN MDR1 CDNA CONFERS MULTIDRUG RESISTANCE AND POLARIZED EXPRESSION OF P-GLYCOPROTEIN IN MDCK CELLS
PASTAN, I
GOTTESMAN, MM
UEDA, K
LOVELACE, E
RUTHERFORD, AV
WILLINGHAM, MC
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (12) : 4486 - 4490
[24] Synthesis and biological evaluation of dihydrobenzofuran lignans and related compounds as potential antitumor agents that inhibit tubulin polymerization
Pieters, L
Van Dyck, S
Gao, M
Bai, RL
Hamel, E
Vlietinck, A
Lemière, G
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (26) : 5475 - 5481
[25] RAO CV, 1993, CANCER RES, V53, P4182
[26] Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure-Activity Relationships
Razzaghi-Asl, N.
Garrido, J.
Khazraei, H.
Borges, F.
Firuzi, O.
[J]. CURRENT MEDICINAL CHEMISTRY, 2013, 20 (36) : 4436 - 4450
[27] Pharmacokinetic, Antiproliferative and Apoptotic Effects of Phenolic Acids in Human Colon Adenocarcinoma Cells Using In Vitro and In Silico Approaches
Rosa, Lana de Souza
Jordao, Nathallia Araujo
Pereira Soares, Nathalia da Costa
de Mesquita, Joelma Freire
Monteiro, Mariana
Teodoro, Anderson Junger
[J]. MOLECULES, 2018, 23 (10):
[28] Comparison of the antimelanogenic effects of p-coumaric acid and its methyl ester and their skin permeabilities
Song, Kyosun
An, Sang Mi
Kim, Mijin
Koh, Jae-Sook
Boo, Yong Chool
[J]. JOURNAL OF DERMATOLOGICAL SCIENCE, 2011, 63 (01) : 17 - 22
[29] Lower antioxidative capacity of multidrug-resistant cancer cells confers collateral sensitivity to protoflavone derivatives
Stankovic, Tijana
Danko, Balazs
Martins, Ana
Dragoj, Miodrag
Stojkovic, Sonja
Isakovic, Aleksandra
Wang, Hui-Chun
Wu, Yang-Chang
Hunyadi, Attila
Pesic, Milica
[J]. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2015, 76 (03) : 555 - 565
[30] Hydroxycinnamic Acids and Their Derivatives: Cosmeceutical Significance, Challenges and Future Perspectives, a Review
Taofiq, Oludemi
Gonzalez-Paramas, Ana M.
Barreiro, Maria Filomena
Ferreira, Isabel C. F. R.
[J]. MOLECULES, 2017, 22 (02):

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