Sintesis Hidroksikumarin dan Hasil Aldol Kondensasinya serta Uji Aktivitasnya sebagai Senyawa Antikanker

Zidhandika Nagita Putra, Prof. Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.; Dr. Endang Astuti, M.Si.

2026 | Skripsi | KIMIA

Penelitian ini melaporkan sintesis senyawa hidroksikumarin serta produk aldol kondensasinya sebagai kandidat antikanker. Tujuan penelitian ini adalah melakukan sintesis senyawa hidroksikumarin yang dilanjutkan dengan reaksi aldol kondensasinya menggunakan metoksibenzaldehida serta menentukan nilai IC₅₀ dari semua produk sebagai agen antikanker. Sintesis hidroksikumarin dilakukan melalui reaksi kondensasi Knoevenagel antara 2,4-dihidroksibenzaldehida dan etil asetoasetat menggunakan basa piperidin dengan metode sonikasi. Kemudian reaksi kondensasi Claisen-Schmidt antara hidroksikumarin dengan 4-metoksibenzaldehida dan 3,4-dimetoksi benzaldehida dilakukan pada suhu ruang menggunakan basa NaOH. Produk sintesis dikarakterisasi menggunakan uji titik leleh, TLC Scanner, spektroskopi FTIR, ¹H-NMR, dan ¹³C-NMR. Aktivitas antikanker diuji secara in vitro terhadap sel T47D, MCF-7, dan WiDr serta sel Vero menggunakan metode MTT.

Senyawa hidroksikumarin diperoleh sebagai padatan berwarna kuning kecoklatan dengan persen hasil 76?n titik leleh 234-235 ?. Reaksi aldol kondensasi terhadap hidroksikumarin menghasilkan senyawa A ((1E,4E)-1-(2,4-dihidroksifenil)-5-(4-metoksifenil)penta-1,4-dien-3-on) berupa padatan berwarna merah bata dengan persen hasil 32% serta titik lelehnya 205,7-207,1 ?, sedangkan senyawa B ((1E,4E)-1-(2,4-dihidroksifenil)-5-(3,4-dimetoksifenil)penta-1,4-dien-3-on)) berwujud padatan coklat tua dengan persen hasil 36?n titik leleh 218,6-220,3 ?. Hasil uji sitotoksisitas menunjukkan bahwa senyawa A dan B memiliki aktivitas antikanker yang lebih tinggi dibandingkan hidroksikumarin dengan nilai IC₅₀<20>A menunjukkan aktivitas terbaik dengan nilai IC₅₀ masing-masing 7,06 dan 10,22 ?g/mL terhadap sel T47D dan MCF-7, serta indeks selektivitas 1,96 dan 1,46.

This study reports the synthesis of hydroxycoumarin compound and its aldol condensation products as potential anticancer agents. This research aims to synthesize hydroxycoumarin, perform its aldol condensation reaction with methoxybenzaldehyde, and determine the IC₅₀ values of all synthesized products as anticancer agents. The hydroxycoumarin was synthesized via a Knoevenagel condensation reaction between 2,4-dihydroxybenzaldehyde and ethyl acetoacetate using piperidine as a base under sonication. Subsequently, Claisen-Schmidt condensation reactions between hydroxycoumarin and 4-methoxybenzaldehyde or 3,4-dimethoxybenzaldehyde were performed at room temperature using NaOH as the base. The synthesized products were characterized by melting point analysis, TLC Scanning, FTIR, ¹H-NMR and ¹³C-NMR spectroscopy. Anticancer activity was evaluated in vitro against T47D, MCF-7, and WiDr cancer cells, as well as Vero cells, using the MTT assay.

Hydroxycoumarin compound was obtained as a yellowish-brown solid with a yield of 76% and a melting point of 234-235 ?. The aldol condensation reaction of hydroxycoumarin produced compound A ((1E,4E)-1-(2,4-dihydroxyphenyl)-5-(4-methoxyphenyl)penta-1,4-dien-3-one) as a brick-red solid with a yield of 32% and a melting point of 205.7-207.1 ?, while compound B ((1E,4E)-1-(2,4-dihydro xyphenyl)-5-(3,4-dimethoxyphenyl)penta-1,4-dien-3-one) was obtained as a dark brown solid with a yield of 36%  and a melting point of 218.6-220.3 ?. The cytotoxicity tests showed that compounds A and B exhibited higher anticancer activity than hydroxycoumarin, with IC₅₀ values below 20 ?g/mL. Compound A demonstrated the best activity, with IC₅₀ values of 7.06 and 10.22 ?g/mL against T47D and MCF-7 cells, respectively, and selectivity indices of 1.96 and 1.46.

Kata Kunci : aldol, antikanker, kumarin, MTT assay.