Preprint Article Version 1 This version is not peer-reviewed

Chemical Synthesis, Efficacy and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds

Version 1 : Received: 8 November 2019 / Approved: 10 November 2019 / Online: 10 November 2019 (10:10:15 CET)

How to cite: Niyibizi, J.B.; Kirira, P.G.; Kimani, F.T.; Oyatsi, F.; Ng’ang’a, J.K. Chemical Synthesis, Efficacy and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds. Preprints 2019, 2019110104 (doi: 10.20944/preprints201911.0104.v1). Niyibizi, J.B.; Kirira, P.G.; Kimani, F.T.; Oyatsi, F.; Ng’ang’a, J.K. Chemical Synthesis, Efficacy and Safety of Antimalarial Hybrid Drug Comprising of Sarcosine and Aniline Pharmacophores as Scaffolds. Preprints 2019, 2019110104 (doi: 10.20944/preprints201911.0104.v1).

Abstract

Background: Reducing the impact of malaria is a key to achieving the sustainable development goals which are geared towards eradicating the disease. The main objective of this study was to synthesize, determine the efficacy and safety of antiplasmodial hybrid drug comprising of sarcosine and aniline derivative for management of plasmodial infections. Results: The hybrid drug was synthesized by adding thionyl chloride to sarcosine in order to form acyl chloride which was then added to aniline to form sarcosine-aniline hybrid molecule. The IC50 of sarcosine-aniline hybrid was 44.80 ± 4.70 ng/ml compared to that of aniline derivative which was 22.86 ± 1.26 ng/ml. The IC50 of control drugs were 2.63 ± 0.38 ng/ml, 5.69 ± 0.39 ng/ml for artesunate and chloroquine respectively. There was a significant difference between IC50 of sarcosine-aniline hybrid and aniline derivative (P<0.05). There was also a significant difference between sarcosine-aniline hybrid and standard drugs used to treat malaria including artesunate and chloroquine (P<0.05). The ED50 of sarcosine-aniline hybrid drug was 6.49mg/kg compared to that of aniline derivative which was 3.61mg/kg. The ED50 of control drugs were 3.56 mg/kg, 2.94mg/kg and 1.78 mg/kg for artesunate-aniline hybrid, artesunate and chloroquine respectively. There was a significant difference (P<0.05) between ED50 of sarcosine-aniline hybrid and both controls such as aniline derivative, artesunate, artesunate-aniline hybrid and chloroquine. Cytotoxicity results revealed that sarcosine-aniline hybrid was safe to vero cells with a CC50 of 50.18±3.53µg/ml. Sarcosine-aniline hybrid was significantly less toxic compared to artesunate, chloroquine and doxorubicin. Sarcosine-aniline hybrid was also safe to mice. Conclusion: Therefore, covalent bitherapy should be used in drug development for drug resistance mitigation.

Subject Areas

chemical synthesis; IC50; ED50; CC50; antimalarial resistance; sarcosine-aniline hybrid drug

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