synthesis and antimalarial evaluation of cyclic β-amino acid-containing dipeptides合成和抗疟评价循环β-amino acid-containing二肽.pdf

Molecules 2008, 13, 432-443 molecules ISSN 1420-3049 © 2008 by MDPI /molecules Full Paper Synthesis and Antimalarial Evaluation of Cyclic β-Amino Acid-Containing Dipeptides 1 2 1 Manisha Sathe , Duraipandian Thavaselvam , Ashish Kumar Srivastava and Mahabir Parshad Kaushik 1,* 1 Discovery Center, Defence R D Establishment, Jhansi Road, Gwalior 474002, India 2 Microbiology Division, Defence Research and Development Establishment, Gwalior-474002, India * Author to whom correspondence should be addressed; E-mail: mpkaushik@ Received: 31 January 2008; in revised form: 11 February 2008 / Accepted: 15 February 2008 / Published: 18 February 2008 Abstract: This paper describes an efficient synthesis and the antiparasitic evaluation of cyclic β-amino acid-containing dipeptides 3.1-3.6 and 4.1-4.5. The antimalarial properties of all these dipeptides have been evaluated in vitro against Plasmodium falciparum and in vivo against Plasmodium berghai. Compounds 4.4 and 4.5 have been found to be very effective in this respect, with IC50 values of 3.87 and 3.64 μg/mL in the in vitro test, while 4.5 has also been found to be active in the in vivo evaluation. Keywords: β-Lactam; β-amino acid; antimalarial; Plasmodium falciparum; Plasmodium berghai Introduction Malaria is one of the most important parasitic diseases of humans due to its high morbidity and mortality [1]. According to WHO,