Multicomponent Access to novel Proline/Cyclized Cysteine Tethered Monastrol Conjugates as Potential Anticancer Agents

Publication date: Available online 18 January 2019Source: Journal of Saudi Chemical SocietyAuthor(s): M. Shaheer Malik, Zaki S. Seddigi, Shaik Bajee, Shaik Azeeza, Syed Riyaz, Saleh A. Ahmed, Ismail I Althagafi, Qazi M. Sajid Jamal, Ahmed KamalAbstractThe versatility of multicomponent Biginelli 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 exhibits 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.
Source: Journal of Saudi Chemical Society - Category: Chemistry Source Type: research