Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies
We report herein the synthesis, docking studies and biological evaluation of a series of new 4-chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol analogues (<b>6a-h</b>). The new compounds were designed based on the oxadiazole-linked aryl core of tubulin inhibitors of IMC-038525 and IMC...
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MDPI AG
2023-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/16/6086 |
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| author | Obaid Afzal Amena Ali Abuzer Ali Abdulmalik Saleh Alfawaz Altamimi Manal A. Alossaimi Md Afroz Bakht Salahuddin Mubarak A. Alamri Md. Faiyaz Ahsan Mohamed Jawed Ahsan |
| author_facet | Obaid Afzal Amena Ali Abuzer Ali Abdulmalik Saleh Alfawaz Altamimi Manal A. Alossaimi Md Afroz Bakht Salahuddin Mubarak A. Alamri Md. Faiyaz Ahsan Mohamed Jawed Ahsan |
| author_sort | Obaid Afzal |
| collection | DOAJ |
| description | We report herein the synthesis, docking studies and biological evaluation of a series of new 4-chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol analogues (<b>6a-h</b>). The new compounds were designed based on the oxadiazole-linked aryl core of tubulin inhibitors of IMC-038525 and IMC-094332, prepared in five steps and further characterized via spectral analyses. The anticancer activity of the compounds was assessed against several cancer cell lines belonging to nine different panels as per National Cancer Institute (NCI US) protocol. 4-Chloro-2-((5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (<b>6h</b>) demonstrated significant anticancer activity against SNB-19 (PGI = 65.12), NCI-H460 (PGI = 55.61), and SNB-75 (PGI = 54.68) at 10 µM. The compounds were subjected to molecular docking studies against the active site of the tubulin–combretastatin A4 complex (PDB ID: 5LYJ); they displayed efficient binding and ligand <b>4h</b> (with docking score = −8.030 kcal/mol) lay within the hydrophobic cavity surrounded by important residues Leu252, Ala250, Leu248, Leu242, Cys241, Val238, Ile318, Ala317, and Ala316. Furthermore, the antibacterial activity of some of the compounds was found to be promising. 4-Chloro-2-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (<b>6c</b>) displayed the most promising antibacterial activity against both Gram-negative as well as Gram-positive bacteria with MICs of 8 µg/mL and a zone of inhibition ranging from 17.0 ± 0.40 to 17.0 ± 0.15 mm at 200 µg/mL; however, the standard drug ciprofloxacin exhibited antibacterial activity with MIC values of 4 µg/mL. |
| first_indexed | 2024-03-10T23:41:11Z |
| format | Article |
| id | doaj.art-160ce12c4fcd4f74bec5d4b5e4c4f481 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T23:41:11Z |
| publishDate | 2023-08-01 |
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| series | Molecules |
| spelling | doaj.art-160ce12c4fcd4f74bec5d4b5e4c4f4812023-11-19T02:24:38ZengMDPI AGMolecules1420-30492023-08-012816608610.3390/molecules28166086Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical StudiesObaid Afzal0Amena Ali1Abuzer Ali2Abdulmalik Saleh Alfawaz Altamimi3Manal A. Alossaimi4Md Afroz Bakht5Salahuddin6Mubarak A. Alamri7Md. Faiyaz Ahsan8Mohamed Jawed Ahsan9Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Chemistry, College of Science and Humanity Studies, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutical Chemistry, Noida Institute of Engineering and Technology, (Pharmacy Institute), Knowledge Park-2, Greater Noida 201 306, IndiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Chemistry, Bihar National College, Patna 800 004, IndiaDepartment of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Jaipur 302 039, IndiaWe report herein the synthesis, docking studies and biological evaluation of a series of new 4-chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol analogues (<b>6a-h</b>). The new compounds were designed based on the oxadiazole-linked aryl core of tubulin inhibitors of IMC-038525 and IMC-094332, prepared in five steps and further characterized via spectral analyses. The anticancer activity of the compounds was assessed against several cancer cell lines belonging to nine different panels as per National Cancer Institute (NCI US) protocol. 4-Chloro-2-((5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (<b>6h</b>) demonstrated significant anticancer activity against SNB-19 (PGI = 65.12), NCI-H460 (PGI = 55.61), and SNB-75 (PGI = 54.68) at 10 µM. The compounds were subjected to molecular docking studies against the active site of the tubulin–combretastatin A4 complex (PDB ID: 5LYJ); they displayed efficient binding and ligand <b>4h</b> (with docking score = −8.030 kcal/mol) lay within the hydrophobic cavity surrounded by important residues Leu252, Ala250, Leu248, Leu242, Cys241, Val238, Ile318, Ala317, and Ala316. Furthermore, the antibacterial activity of some of the compounds was found to be promising. 4-Chloro-2-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (<b>6c</b>) displayed the most promising antibacterial activity against both Gram-negative as well as Gram-positive bacteria with MICs of 8 µg/mL and a zone of inhibition ranging from 17.0 ± 0.40 to 17.0 ± 0.15 mm at 200 µg/mL; however, the standard drug ciprofloxacin exhibited antibacterial activity with MIC values of 4 µg/mL.https://www.mdpi.com/1420-3049/28/16/6086anticancerantibacterialDNA gyrasemolecular docking1,3,4-oxadiazoletubulin |
| spellingShingle | Obaid Afzal Amena Ali Abuzer Ali Abdulmalik Saleh Alfawaz Altamimi Manal A. Alossaimi Md Afroz Bakht Salahuddin Mubarak A. Alamri Md. Faiyaz Ahsan Mohamed Jawed Ahsan Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies Molecules anticancer antibacterial DNA gyrase molecular docking 1,3,4-oxadiazole tubulin |
| title | Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies |
| title_full | Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies |
| title_fullStr | Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies |
| title_full_unstemmed | Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies |
| title_short | Synthesis and Anticancer Evaluation of 4-Chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol Analogues: An Insight into Experimental and Theoretical Studies |
| title_sort | synthesis and anticancer evaluation of 4 chloro 2 5 aryl 1 3 4 oxadiazol 2 yl amino phenol analogues an insight into experimental and theoretical studies |
| topic | anticancer antibacterial DNA gyrase molecular docking 1,3,4-oxadiazole tubulin |
| url | https://www.mdpi.com/1420-3049/28/16/6086 |
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