Synthesis and biological evaluation of new Camptothecin-like compounds as anticancer agents

被引:1
作者
Madkour, Moustafa M. [1 ,2 ]
Sebastian, Anusha [1 ]
Ramadan, Wafaa S. [1 ]
Menon, Varsha [1 ]
Lozon, Lama [1 ,3 ]
Srikanth, Gourishetty [1 ]
Tarazi, Hamadeh [1 ,4 ]
El-Gamal, Mohammed I. [1 ,4 ]
Al-Tel, Taleb H. [1 ,4 ]
El-Awady, Raafat [1 ,2 ]
机构
[1] Univ Sharjah, Res Inst Med & Hlth Sci, Sharjah 27272, U Arab Emirates
[2] Univ Sharjah, Coll Pharm, Dept Pharm Practice & Pharmacotherapeut, Sharjah 27272, U Arab Emirates
[3] Univ Sharjah, Coll Med, Univ Rd, Sharjah 27272, U Arab Emirates
[4] Univ Sharjah, Coll Pharm, Dept Med Chem, Sharjah 27272, U Arab Emirates
关键词
Camptothecin analogues; Quinolone; Topoisomerases; Cell cycle; Apoptosis; DNA TOPOISOMERASE-I; MISMATCH REPAIR; CELL-CYCLE; MECHANISM; REPLICATION; INHIBITION; COMPLEXES; APOPTOSIS; DESIGN; ARREST;
D O I
10.1016/j.molstruc.2024.141271
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Herein, we report on the synthesis and evaluation of new pentacyclic quinolone analogues as potential Top I inhibitors as potential lead drug candidates for cancer treatment. Among the developed series of compounds, is the isopropyl quinolone derivative 10e that demonstrated effective anticancer activity across various cancer cell lines, while maintaining a safe profile in normal cells. In silico analysis demonstrated the binding of 10e to the Top I/DNA complex. Furthermore, this compound exhibited partial inhibition of both Top I and Top II enzymes, induced G1 phase arrest, and promoted apoptosis in cancer cells. In conclusion, compound 10e exerted potent cytotoxic activity against several cancer types and could be used as a lead for the development of new cancer modality and which warrant further investigations as a potential anticancer agent.
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页数:19
相关论文
共 56 条
[1]   DNA damage signaling in response to 5-fluorouracil in three colorectal cancer cell lines with different mismatch repair and TP53 status [J].
Adamsen, Birgitte L. ;
Kravik, Katherine L. ;
De Angelis, Paula M. .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2011, 39 (03) :673-682
[2]   Divergent Strategy for the Synthesis of Indolopyrazines Fused to Benzopyrimidinones and Benzimidazoles: Identification of Antiproliferative Molecules [J].
Alkubaisi, Bilal O. ;
Sebastian, Anusha ;
Bauer, Maximilian ;
Sultan, Shaista ;
El-Awady, Raafat ;
Wehbe, Ayeh ;
Yassin, Mariam ;
Vunnam, Srinivasulu ;
El-Gamal, Mohammed I. ;
Al-Tel, Taleb H. .
CHEMISTRYSELECT, 2023, 8 (46)
[3]   Interaction of an anticancer benzopyrane derivative with DNA: Biophysical, biochemical, and molecular modeling studies [J].
Alniss, Hasan Y. ;
Chu, Chen ;
Ramadan, Wafaa S. ;
Msallam, Yousef A. ;
Srinivasulu, Vunnam ;
El-Awady, Raafat ;
Macgregor Jr, Robert B. ;
Al-Tel, Taleb H. .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2023, 1867 (06)
[4]   Design and synthesis of novel 7-ethyl-10-fluoro-20-O-(cinnamic acid ester)-camptothecin derivatives as potential high selectivity and low toxicity topoisomerase I inhibitors for hepatocellular carcinoma [J].
Bai, Yin-Peng ;
Yang, Cheng-Jie ;
Deng, Nan ;
Zhang, Mi ;
Zhang, Zhi-Jun ;
Li, Lei ;
Zhou, Yong ;
Luo, Xiong-Fei ;
Xu, Chuan-Rui ;
Zhang, Bao-Qi ;
Ma, Yue ;
Liu, Ying-Qian .
BIOCHEMICAL PHARMACOLOGY, 2022, 200
[5]   Structural studies of type I topoisomerases [J].
Baker, Nicole M. ;
Rajan, Rakhi ;
Mondragon, Alfonso .
NUCLEIC ACIDS RESEARCH, 2009, 37 (03) :693-701
[6]   Functional interactions and signaling properties of mammalian DNA mismatch repair proteins [J].
Bellacosa, A .
CELL DEATH AND DIFFERENTIATION, 2001, 8 (11) :1076-1092
[7]   Synthesis and Evaluation of New Naphthalene and Naphthoquinone Derivatives as Anticancer Agents [J].
Beretta, Giovanni L. ;
Ribaudo, Giovanni ;
Menegazzo, Ileana ;
Supino, Rosanna ;
Capranico, Giovanni ;
Zunino, Franco ;
Zagotto, Giuseppe .
ARCHIV DER PHARMAZIE, 2017, 350 (01)
[8]  
Bjornsti Mary-Ann, 2019, F1000Res, V8, DOI 10.12688/f1000research.20201.1
[9]   DNA topoisomerases: Structure, function, and mechanism [J].
Champoux, JJ .
ANNUAL REVIEW OF BIOCHEMISTRY, 2001, 70 :369-413
[10]   Synthesis of new indeno[1,2-c]isoquinolines:: Cytotoxic non-camptothecin topoisomerase I inhibitors [J].
Cushman, M ;
Jayaraman, M ;
Vroman, JA ;
Fukunaga, AK ;
Fox, BM ;
Kohlhagen, G ;
Strumberg, D ;
Pommier, Y .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (20) :3688-3698