Sintesis dan Uji Aktivitas Antikanker Klorokumarin dan Klorokumarin-Kalkon Tersubstitusi Metoksi

Muhammad Rizal Mahmudi, Prof. Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.; Dr. Endang Astuti, M.Si.

2025 | Skripsi | KIMIA

Sintesis klorokumarin dan klorokumarin-kalkon serta uji sitotoksisitasnya terhadap sel kanker telah dilakukan. Senyawa klorokumarin disintesis melalui reaksi kondensasi Knoevenagel antara 5-kloro-2-hidroksibenzaldehida dan etil asetoasetat dengan katalis piperidin menggunakan metode grinding. Senyawa kalkon A dan B disintesis melalui reaksi kondensasi Claisen-Schmidt antara klorokumarin dan benzaldehida tersubstitusi metoksi  dengan katalis piperidin dalam pelarut 1-propanol menggunakan metode refluks. Semua produk dikarakterisasi dengan uji titik leleh, GC-MS, ATR-IR, 1H-NMR, dan 13C-NMR. Senyawa hasil sintesis diuji sitotoksisitasnya terhadap sel kanker payudara (T47D dan MCF-7), serviks (HeLa), kolon (WiDr), dan sel normal (Vero).

Senyawa klorokumarin diperoleh sebagai padatan putih dengan persen hasil 77?n titik leleh 205,8-207,1 °C. Kalkon A dihasilkan sebagai padatan kuning pucat dengan persen hasil 46?n titik leleh 195,3-196,5 °C, sedangkan kalkon B diperoleh sebagai padatan kuning cerah dengan persen hasil 33?n titik leleh 240,2-241,8 °C. Pengujian sitotoksisitas menunjukkan bahwa kalkon A memiliki aktivitas antikanker paling kuat, terutama terhadap sel kanker serviks (HeLa) dan sel kanker kolon (WiDr). Nilai IC50 dan indeks selektivitas (SI) dari kalkon A terhadap sel kanker serviks (HeLa) yaitu 35,08 ?g/mL dan 9,93, sedangkan terhadap sel kanker kolon (WiDr) yaitu 55,23 ?g/mL dan 6,31. Hasil ini menunjukkan bahwa kalkon A memiliki potensi menjanjikan sebagai agen antikanker, khususnya untuk pengobatan kanker serviks dan kanker kolon.

The synthesis of chlorocoumarin and chlorocoumarin-chalcone derivatives was successfully carried out, followed by the evaluation of their cytotoxic activity against cancer cell lines. The chlorocoumarin was synthesized via a Knoevenagel condensation reaction between 5-chloro-2-hydroxybenzaldehyde and ethyl acetoacetate, catalyzed by piperidine using a grinding method. Chalcones A and B were obtained through a Claisen-Schmidt condensation reaction between chlorocoumarin and methoxy-substituted benzaldehydes in the presence of piperidine as a catalyst, using 1-propanol as solvent under reflux conditions. All synthesized products were characterized using melting point testing, GC-MS, ATR-IR, 1H-NMR, and 13C-NMR spectroscopy. Cytotoxicity assays were performed against breast cancer cell lines (T47D and MCF-7), cervical cancer cells (HeLa), colon cancer cells (WiDr), and normal cells (Vero).

The chlorocoumarin was obtained as a white solid with a yield of 77% and a melting point of 205.8-207.1 °C. Chalcone A was isolated as a pale yellow solid with a yield of 46% and a melting point of 195.3-196.5 °C, while chalcone B was obtained as a bright yellow solid with a yield of 33% and a melting point of 240.2-241.8 °C. Cytotoxicity testing revealed that Chalcone A exhibited the most potent anticancer activity, particularly against cervical cancer (HeLa) and colon cancer (WiDr) cells. The IC50 and selectivity index (SI) values of chalcone A against HeLa cells were 35.08 ?g/mL and 9.93, respectively, while against WiDr cells, the values were 55.23 ?g/mL and 6.31. These findings suggest that chalcone A shows promising potential as an anticancer agent, especially for the treatment of cervical and colon cancers.

Kata Kunci : antikanker, kalkon, klorokumarin, sitotoksisitas