Page 110 - Pharma News Letter - Vol2 Issue 1

Chapter V

Design, Synthesis, And Repurposing Of Rosmarinic Acid-Β-
Amino-Α-Ketoamide Hybrids As Antileishmanial Agents

Pharmaceuticals. 2023; 16(11): 1594.
------------------------------------------------------------------------------------
Ahmed H.e. Hassan, Waleed A. Bayoumi, Selwan M El-Sayed, Trong-Nhat Phan,
Taegeun Oh, Gyeongpyo Ham, Kazem Mahmoud, Joo Hwan No, Yong Sup Lee

Abstract

A series of rosmarinic acid-β-amino-α-ketoamide hybrids were synthesized and rationally
repurposed towards the identification of new antileishmanial hit compounds. Two hybrids, 2g
and 2h, showed promising activity (IC50 values of 9.5 and 8.8 μM against Leishmania donovani
promastigotes, respectively). Their activities were comparable to erufosine. In addition,
cytotoxicity evaluation employing human THP-1 cells revealed that the two hybrids 2g and
2h possess no cytotoxic effects up to 100 µM, while erufosine possessed cytotoxicity with
CC50 value of 19.4 µM. In silico docking provided insights into structure–activity relationship
emphasizing the importance of the aliphatic chain at the α-carbon of the cinnamoyl carbonyl
group establishing favorable binding interactions with LdCALP and LARG in both hybrids 2g
and 2h. In light of these findings, hybrids 2g and 2h are suggested as potential safe antileishmanial
hit compounds for further development of anti-leishmanial agents.

Reference:

https://doi.org/10.3390/ph16111594

110 Faculty of Pharmacy Newsletter