Abstract

Ade Arsianti^1,3, Hendry Astuti², Fadilah^1,3, Daniel Martin Simadibrata⁵, Zoya Marie Adyasa⁵, Daniel Amartya⁵, Anton Bahtiar⁴, Hiroki Tanimoto⁶ and Kiyomi Kakiuchi⁶

DOI : http://dx.doi.org/10.13005/ojc/340207

Malaria is an infectious disease caused by parasite Plasmodium which has a high prevalence in tropical and subtropical countries. In Indonesia, around 396 districts  are found as endemic area for malaria, with the highest Annual Parasitic Incidence (API) in Papua, West Papua and East Nusa Tenggara. Currently, treatment for malaria caused by parasite Plasmodium falciparum relies on the use of 4-aminoquinoline or synergistic combinations of antifolates and sulfamethoxazole-trimethoprim. However, this treatment is no longer effective and develop resistancy. This fact suggesting the new antimalarial activity that is more effective and safer are needed. Previous research revealed that gallic acid and its alkyl esters derivatives exhibited antimalarial activity. This study is aimed to synthesize alkyl esters gallate and determine its in vitro antimalarial activity against parasite Plasmodium falciparum. Fourteen compounds of alkyl esters gallate were synthesized by esterification of the carboxyl group of gallic acid with a series of alkyl alcohols, as well as methoxylation of the hydroxy groups on the aromatic ring of gallic acid. Antimalarial activity of the synthesized alkyl esters gallate were expressed by IC₅₀ value, with gallic acid as an original compound and artemisin as a positive control.  Compared to gallic acid, eleven synthesized compounds of alkyl esters gallate, have a greater antimalarial activity against Plasmodium falciparum. On the other hand, three compounds, that are propyl gallate, butyl gallate and trimethoxy methyl gallate, showed a lower antimalarial activity. Moreover, compared to gallic acid (IC₅₀ : 194.86 mM) and artemisin (IC₅₀ : 0.5 mM), two synthesized compounds of alkyl gallates, namely methyl gallate and hexyl gallate exhibited the stronger antimalarial activity against Plasmodium falciparum, with IC₅₀ value of 0.03 mM and 0.11 mM, respectively. Our result clearly demonstrated that methyl gallate and hexyl gallate as a promising candidate for the new antimalarial agents.

Synthesis; alkyl ester gallate; in vitro; antimalarial; Plasmodium falciparum

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