Abstract
In this study, for the first time, we have used Citrus macroptera juice to synthesize dihydropyrimidine (DHPM) derivatives via the Biginelli reaction, which showed better yield, shorter reaction time, and did not require an organic solvent for the reaction. A series of DHPM derivatives were synthesized, and characterized, and structural analysis was achieved through SCXRD & Hirshfeld surface analysis. We observed that these synthesized dihydropyrimidine (DHPM) derivatives showed C–H⋯π, C–H⋯O, C–H⋯N, C–H⋯C, lone pair⋯π, π⋯π, etc. interactions. We also performed in silico studies for their inhibitory activities against human kinesin Eg5 enzyme, and the cytotoxic activity of the synthesized compounds was carried out against A549 lung adenocarcinoma cells. In silico analysis demonstrated that compounds with a chloro-group at the 3- or 4-position in the substituted ring of DHPM showed higher binding affinity for the human kinesin Eg5 enzyme (−7.9 kcal mol−1) than the standard drug monastrol (−7.8 kcal mol−1). Furthermore, in vitro cellular studies revealed that compounds with a chloro-group at the 3- or 4-position in the substituted ring of DHPM induced significant cell death in human A549 lung adenocarcinoma cells. This result indicates that a deactivating group (chlorine) at the 3- or 4-position in the substituted ring of DHPM might be a promising anticancer drug candidate for treating different types of cancers, particularly cancer of the lung.
Highlights
Cancer accounts for the second leading cause of death worldwide despite many breakthroughs for cancer treatment
A series of DHPM derivatives (1.1–1.5) were synthesized using urea, ethyl acetoacetate with electron-rich and electronde cient aromatic aldehydes through green catalyzed reaction given in Scheme 1
First-time Citrus macroptera juices were used as bio-catalyst for the synthesized DHPM derivatives, which showed better yield and shorter duration
Summary
Cancer accounts for the second leading cause of death worldwide despite many breakthroughs for cancer treatment. DHPM classes of compounds are structural analogs of monastrol. Several studies revealed that DHPMs inhibitory action on human kinesin Eg5 leads to a mitotic arrest resulting in apoptosis.[9] This was the main action in apoptosis described for. Monastrol has inspired medicinal chemists to design new anticancer agents based on the DHPM scaffold or its modi cation with different substituents. Our rst effort was to understand non-covalent interactions in the synthesized DHPM derivatives and the effect of substituents with different electronic environments on conformations of some selected synthesized molecules. We carried out cytotoxic studies of these compounds in the lung adenocarcinoma (A549) cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
