Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives
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 antip...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Journal of King Saud University: Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1018364722001847 |
| _version_ | 1811256179723075584 |
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| author | Abdulrashid Umar Hassan M. Faidallah Qamar Uddin Ahmed Khalid.A. Alamry Sayeed Mukhtar Meshari A. Alsharif Syed Najmul Hejaz Azmi Humaira Parveen Zainul Amiruddin Zakaria Mostafa A. Hussien |
| author_facet | Abdulrashid Umar Hassan M. Faidallah Qamar Uddin Ahmed Khalid.A. Alamry Sayeed Mukhtar Meshari A. Alsharif Syed Najmul Hejaz Azmi Humaira Parveen Zainul Amiruddin Zakaria Mostafa A. Hussien |
| author_sort | Abdulrashid Umar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T17:36:13Z |
| format | Article |
| id | doaj.art-d18931a5e7aa4ca3a763cd3a0402367d |
| institution | Directory Open Access Journal |
| issn | 1018-3647 |
| language | English |
| last_indexed | 2024-04-12T17:36:13Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of King Saud University: Science |
| spelling | doaj.art-d18931a5e7aa4ca3a763cd3a0402367d2022-12-22T03:22:58ZengElsevierJournal of King Saud University: Science1018-36472022-06-01344102003Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivativesAbdulrashid Umar0Hassan M. Faidallah1Qamar Uddin Ahmed2Khalid.A. Alamry3Sayeed Mukhtar4Meshari A. Alsharif5Syed Najmul Hejaz Azmi6Humaira Parveen7Zainul Amiruddin Zakaria8Mostafa A. Hussien9Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria 21526, EgyptDrug Discovery and Synthetic Chemistry Research Group, Department of Pharmaceutical Chemistry, Kulliyyah of Pharmacy, International Islamic University Malaysia, 25200 Kuantan, Pahang DM, Malaysia; Corresponding authors.Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi ArabiaDepartment of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi ArabiaChemistry Department, Faculty of Applied Science, Umm Al-Qura University, Makkah, Saudi ArabiaUniversity of Technology and Applied Sciences, Applied Sciences Department (Chemistry Section), Higher College of Technology Muscat, P. O. Box 74, Al-Khuwair 133, Sultanate of OmanDepartment of Chemistry, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu 88400, Sabah, Malaysia; Corresponding authors.Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi ArabiaQuinoline 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.http://www.sciencedirect.com/science/article/pii/S1018364722001847QuinolinesBenzoquinoline derivativesCytotoxicityMolecular dockingComputational studies |
| spellingShingle | Abdulrashid Umar Hassan M. Faidallah Qamar Uddin Ahmed Khalid.A. Alamry Sayeed Mukhtar Meshari A. Alsharif Syed Najmul Hejaz Azmi Humaira Parveen Zainul Amiruddin Zakaria Mostafa A. Hussien 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 Quinolines Benzoquinoline derivatives Cytotoxicity Molecular docking Computational studies |
| title | Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives |
| title_full | Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives |
| title_fullStr | Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives |
| title_full_unstemmed | Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives |
| title_short | Design, synthesis, in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives |
| title_sort | design synthesis in vitro antiproliferative effect and in situ molecular docking studies of a series of new benzoquinoline derivatives |
| topic | Quinolines Benzoquinoline derivatives Cytotoxicity Molecular docking Computational studies |
| url | http://www.sciencedirect.com/science/article/pii/S1018364722001847 |
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