Multicomponent access to novel proline/cyclized cysteine tethered monastrol conjugates as potential anticancer agents

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...

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Bibliographic Details
Published in:Journal of Saudi Chemical Society 2019-05, Vol.23 (4), p.503-513
Main Authors: Shaheer Malik, M., Seddigi, Zaki S., Bajee, Shaik, Azeeza, Shaik, Riyaz, Syed, Ahmed, Saleh A., Althagafi, Ismail I., Sajid Jamal, Qazi M., Kamal, Ahmed
Format: Article
Language:English
Subjects:
Amino acids
Anticancer agents
Docking studies
Monastrol
Multicomponent Biginelli’s reaction
الأدوية المضادة للأورام
البرولين
البوليمرات المترافقة
السرطان
السيستئين
العلاج المناعي
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Summary: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.
ISSN:1319-6103
DOI:10.1016/j.jscs.2019.01.003