Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives

Journal of King Saud University: Science

Khalid.A. Alamry¹  Syed Najmul Hejaz Azmi²  Mostafa A. Hussien³  Hassan M. Faidallah⁴  Sayeed Mukhtar⁵  Abdulrashid Umar⁵  Meshari A. Alsharif⁶  Zainul Amiruddin Zakaria⁶  Qamar Uddin Ahmed⁷  Humaira Parveen⁸ 

[1] Corresponding authors.;Chemistry Department, Faculty of Applied Science, Umm Al-Qura University, Makkah, Saudi Arabia;Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia;Department of Chemistry, Faculty of Science, Alexandria University, Alexandria 21526, Egypt;Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia;Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia;Drug Discovery and Synthetic Chemistry Research Group, Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang DM, Malaysia;University of Technology and Applied Sciences, Applied Sciences Department (Chemistry Section), Higher College of Technology Muscat, P. O. Box 74, Al-Khuwair 133, Sultanate of Oman;

关键词: Quinolines;    Benzoquinoline derivatives;    Cytotoxicity;    Molecular docking;    Computational studies;   

DOI  :  

来源: DOAJ

【 摘 要 】

Quinoline derivatives have been reported to possess multi-therapeutic potential owing to the manifestations of different pharmacological effects. The current research work describes about the design and synthesis of a series of novel benzoquinoline analogues with an objective to evaluate their antiproliferative structure–activity relationship against colon, breast and hepatocellular cancers. Upon synthesis, all derivatives’ chemical structures were elucidated through FTIR, 1HNMR and 13CNMR spectroscopic analysis. All derivatives were investigated for their in vitro anti-proliferative property against three different cancer cell lines (viz., colon carcinoma HT29, Caucasian breast adenocarcinoma MCF7, hepatocellular carcinoma HepG2) and a normal non-transformed human foreskin fibroblast Hs27 cell line. All derivatives demonstrated varied degrees of strong anticancer effect against all of the cell lines with the 2-Amino-4-(4-nitrophenyl)-5,6-dihydrobenzo[h]quinoline-3-carbonitrile (CNMP, 2) exhibited the most potent antiproliferative effect viz. LC50 21.23 μM for breast, 8.24 μM for colon, and 26.15 μM for the hepatocellular, respectively. Molecular docking studies against all the the target crystal structures of cancer proteins (1HK7, 3EQM, 3IG7 and 4FM9) revealed significant binding affinities via hydrophobic and H-bonding interactions with all the compounds in conformity with the wet lab results. CNMP showed the highest binding energy of −7.55 in the HT29, −6.9 (both in MCF7 HepG2) kcal/mol. Based on the results obtained from wet lab and dry lab experiments, it can be proposed that CNMP might prove to be a potential lead structure for the design and synthesis of more potent anticancer candidates.

【 授权许可】

Unknown