ORIENTAL JOURNAL OF CHEMISTRY www.orientjchem.org An International Open Free Access, Peer Reviewed Research Journal ISSN: 0970-020 X CODEN: OJCHEG 2018, Vol. 34, No.(5): Pg. 2643-2650 This is an Open Access article licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/), which permits unrestricted Non Commercial use, distribution and reproduction in any medium, provided the original work is properly cited. Novel Cinchona Alkaloid Derivatives as Potential Antimalarial Agents Through Receptor–Inhibitor Interaction Fingerprint and Biosynthesis Design ROSMALENA 1 , VIVITRI D. PRASASTY 2 and MUHAMMAD HANAFI 3 * 1 Department of Medical Chemistry, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. 2 Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia. 3 Research Center for Chemistry, Indonesian Institute of Sciences, Puspiptek, Serpong, Indonesia. *Corresponding author E-mail: hanafi124@yahoo.com http://dx.doi.org/10.13005/ojc/340556 (Received: January 18, 2018; Accepted: August 25, 2018) ABSTRACT Malaria parasites have become the major health threat in increasing resistance toward common antimalarial drugs and become prime factors causing the strength of the disease. The objective of this study was investigating novel cinchona alkaloid derivatives (CADs) as potential antimalarial agents through molecular docking, pharmacopore modeling and biosynthesis design. Protein structure and cinchona alkaloid derivative structures were taken and performed for molecular interaction studies, pharmacophore modeling and mapping the binding modes of receptor-inhibitors which may increase the possibility of success rate in finding potential antimalarial candidates. Here, we report the greatest prospective inhibitor of Plasmodium falciparum (Pf falcipain-2, PDB ID code 2 ghu ) falcipain-2 is cinchonidine salicylate (-9.1 kcal/mol) through molecular docking approach. This compound exhibited distortion free of Lipinski`s rule. Hence, cinchonidine salicylate showed the most potential compound as antimalarial inhibitor over other cinchona alkaloid derivatives. Eventually, we construct biosynthesis pathways by using iron oxide nanoparticle (IONP) that could act as a coated nanoparticle to the natural bioactives to acquire optimum yield of the product by making coated nanoparticle with CADs which are powerful biosynthesis application in green environment of aqueous solution. Keywords: Cinchona alkaloid derivatives, Antimalaria, Molecular docking, Biosynthesis. INTRODUCTION Malaria is an endemic disease caused by parasitic infection which influencing over than 224 million people and effecting mortality approximately 700,000 every year in the world 1 . According to 41% of total world’s population, malaria is spreading in some areas of Africa, Asia, America, Hispaniola, and Oceania 2-4 , where Africa is the highest malarial prevalent area of the world annually 5-7 . Malaria is known as a vector born disease transmitted by female Anopheles mosquito and parasitic infection mostly caused by five species, including Plasmodium ovale, Plasmodium vivax, Plasmodium falciparum, Plasmodium malariae and Plasmodium knowlesi 8 .