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SINTESIS KLORO-PIRAZOLINA TERSUBSTITUSI PADA NITROGEN DAN UJI AKTIVITASNYA SEBAGAI ANTIMALARIA

MINANDRE WIRATAMA, Dra. Tutik Dwi Wahyuningsih M.Si., Ph.D.; Dr. Winarto Haryadi M.Si.

2020 | Tesis | MAGISTER KIMIA

Telah dilakukan sintesis turunan pirazolina serta uji aktivitasnya sebagai antimalaria. Penelitian ini bertujuan untuk menemukan turunan senyawa kloropirazolina yang potensial sebagai senyawa aktif antimalaria. Penelitian dilakukan melalui dua tahapan, yaitu: sintesis senyawa turunan N-substituen pirazolina dan uji aktivitasnya sebagai senyawa antimalaria. Sintesis pirazolina A-D dilakukan dengan mereaksikan 4-kloro-(3',4'-dimetoksi)-kalkon dan turunan hidrazina, yaitu formil hidrazina, benzoil hidrazina, fenil hidrazina dan klorofenil hidrazina. Reaksi dilakukan dengan metode konvensional dan sonikasi dalam etanol sebagai pelarut dan dengan adanya asam asetat glasial sebagai katalis untuk menghasilkan 1-formil-(3-(4-klorofenil)-5-(3,4-dimetoksi)-4,5-dihidro-2-pirazolina (pirazolina A), 1-benzoil-(3-(4-klorofenil)-5-(3,4-dimetoksi)-4,5-dihidro-2-pirazolina (pirazolina B), 1-fenil-(3-(4-klorofenil)-5-(3,4-dimetoksi)-4,5-dihidro-2-pirazolina (pirazolina C) dan 1-klorofenil-(3-(4-klorofenil)-5-(3,4-dimetoksi)-4,5-dihidro-2-pirazolina (pirazolina D). Elusidasi struktur seluruh senyawa hasil sintesis dilakukan menggunakan FT-IR, GC-MS, 1H-dan 13C-NMR. Produk hasil sintesis diuji aktivitasnya sebagai senyawa antimalaria secara in vitro terhadap Plasmodium falciparum 3D7. Berdasarkan hasil penelitian diperoleh pirazolina A dan B berupa padatan putih dengan yield berturut-turut 91,27 dan 90,47% dan titik leleh 109-110 dan 101-103 °C, pirazolina C berupa padatan putih kekuningan dengan yield 75,53% dan titik leleh 143-144 °C, sedangkan pirazolina D berupa padatan kuning dengan yield 86,68% dan titik leleh 191-193 °C. Uji aktivitas antimalaria terhadap senyawa pirazolina A-D menghasilkan nilai IC50 berturut-turut 8,25; 2,79; 551,25 dan 272,91 µM. Dapat disimpulkan bahwa perbedaan substituen pada Nitrogen pirazolina memberikan aktivitas sebagai antimalaria yang berbeda dimana pirazolina A dan B dikategorikan senyawa yang aktif sebagai antimalaria. Sebaliknya, pirazolina C dan D dikategorikan senyawa tidak aktif sebagai antimalaria.

Synthesis of pyrazoline derivatives and their activity assay as antimalarial have been carried out. The aim of this study is to discover potent chloropyrazoline derivatives as candidates for active antimalarial compounds. This research was carried out through two main steps, i.e., synthesis of N-substituted pyrazoline derivatives, and its activity assay as antimalarial agents. Synthesis of pyrazoline A-D was carried out by reacting 4-chloro-(3',4'-dimethoxy)-chalcone with hydrazine derivatives, i.e.formyl hydrazine, benzoyl hydrazine, phenyl hydrazine and chlorophenyl hydrazine. The reactions were performed using conventional and sonication methods in ethanol as a solvent and in the presence of glacial acetic acid as a catalyst to produce 1-formyl-(3-(4-chlorophenyl)-5-(3,4-dimethoxy)-4,5-dihydro-2-pyrazoline (pyrazoline A), 1-benzoyl -(3-(4-chlorophenyl)-5-(3,4-dimethoxy)-4,5-dihydro-2-pyrazoline (pyrazoline B), 1-phenyl-(3-(4-chlorophenyl)-5-(3,4-dimethoxy)-4,5-dihydro-2-pyrazoline (pyrazoline C), and 1-chlorophenyl-(3-(4-chlorophenyl)-5-(3,4-dimethoxy)-4,5-dihydro-2-pyrazoline (pyrazoline D). The structure elucidation of all synthesized compounds was confirmed by FT-IR, GC-MS, 1H-and 13-CNMR spectrometers. The synthesized products were tested for its activity as antimalarial compounds in vitro assay against Plasmodium falciparum 3D7. The results showed that pyrazoline A and B were yielded as white solids in 91.27 and 90.47% with m.p 109-110 and 101-103 °C, respectively. Pyrazoline C was obtained as a yellowish-white solid in 75.53% yield with m.p 143-144 °C, while pyrazoline D was yielded as yellow solid in 86.68% and m.p 191-193 °C. Antimalarial activity test of pyrazoline A-D gave IC50 values of 8.25; 2.79; 551.25 and 272.91 µM, respectively. It can be concluded that the differences in substituents of Nitrogen pyrazoline resulted in different antimalarial activities. Pyrazoline A and B were categorized as good antimalarial agents. In contrast, pyrazoline C and D were classified as inactive as antimalarial agents.

Kata Kunci : Kata kunci: N-substituen pirazolina, sonokimia, antimalaria, Plasmodium falciparum 3D7

  1. S2-2020-433833-abstract.pdf  
  2. S2-2020-433833-bibliography.pdf  
  3. S2-2020-433833-tableofcontent.pdf  
  4. S2-2020-433833-title.pdf