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Multicomponent access to novel proline/cyclized cysteine tethered monastrol conjugates as potential anticancer agents |
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| Authors: | M Shaheer Malik Zaki S Seddigi Shaik Bajee Shaik Azeeza Syed Riyaz Saleh A Ahmed Ismail I Althagafi Qazi M Sajid Jamal Ahmed Kamal |
| Institution: | 1. Central Research Laboratories, Faculty of Applied Sciences, Umm Al-Qura University, 21955 Makkah, Saudi Arabia;2. Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, 21955 Makkah, Saudi Arabia;3. Department of Environmental Health, College of Public Health and Health informatics, Umm Al-Qura University, 21955 Makkah, Saudi Arabia;4. Department of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India;5. Department of Health Information Management, College of Applied Medical Sciences, Buraydah Colleges, Al Qassim, Saudi Arabia |
| Abstract: | The versatility of multicomponent Biginelli’s reaction is exploited in the development of proline and cyclized cysteine tethered conjugates of monastrol, a kinesin Eg5 inhibitor. Ten new conjugates are synthesized focusing on structural replacement of the ester moiety (C-5 position) of the monastrol backbone with amino acid based amide moieties. On cytotoxic evaluation, conjugate 24 has shown promising in vitro cytotoxic activity against leukemia. Molecular docking studies revealed that the conjugates 19 and 24 exhibit better interaction at kinesin Eg5 receptor compared to monastrol. Moreover, computational calculations and predictions of important molecular properties suggest that these new amino acid based conjugates could be further improved to provide potential anticancer agents. |
| Keywords: | Corresponding authors Monastrol Amino acids Multicomponent Biginelli’s reaction Anticancer agents Docking studies |
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