SINTESIS NANOSUSPENSI ANALOG KURKUMIN 3,5-BIS(4-METOKSIBENZILIDIN)-4-PIPERIDON, STUDI PENAMBATAN MOLEKUL, DAN SITOTOKSISITAS TERHADAP SEL KANKER MCF-7

Azharu Trisaputra Syaban, Dr. Endang Astuti, M.Si.; Prof. Dr. Winarto Haryadi, M.Si.

2026 | Skripsi | KIMIA

Senyawa analog kurkumin 3,5-bis(4-metoksibenzilidin)-4-piperidon telah disintesis melalui reaksi kondensasi Claisen-Schmidt dalam kondisi basa menggunakan sonikasi. Hasil sintesis analog kurkumin dikarakterisasi dengan ATR-IR, 1H-NMR, 13C-NMR dan diformulasi menjadi nanosuspensi dengan metode nanopresipitasi penguapan pelarut diklorometana sebagai pelarut dan tween 60 sebagai zat penstabil. Senyawa analog kurkumin dan nanosuspensi analog kurkumin dilakukan peninjauan secara farmakokinetik melalui pengujian kestabilan partikel menggunakan PSA-DLS dan ditinjau secara farmakodinamika melalui penambatan molekul terhadap protein ER?, Bcl-2, dan PI3K. Hasil sintesis senyawa analog kurkumin dan sediaan nanosuspensi dilakukan uji aktivitasnya sebagai kandidat senyawa obat kemopreventif kanker payudara pada sel MCF-7. Hasil sintesis senyawa analog kurkumin diperoleh rendemen 84,7?ngan kemurnian 91,6%. Formulasi nanosuspensi analog kurkumin didapatkan ukuran partikel rata-rata sebesar 116 nm dengan nilai polidispersitas 0,3 dan zeta potensial ?52,1 mV. Nanosuspensi analog kurkumin memiliki aktivitas penghambatan sel kanker MCF-7 dan selektivitas yang lebih baik dibandingkan sediaan analog kukumin non-nanosuspensi. Nilai IC50 yang dihasilkan masing-masing 15,01 dan 33,64 ?g mL?1 dengan indeks selektivitas masing-masing 20,4 dan 1,75. Sediaan nanosuspensi analog kurkumin memiliki nilai penghambatan yang lebih baik dibandingkan kurkumin dikarenakan adanya peningkatan kelarutan dan rendahnya nilai afinitas interaksi dengan residu asam amino spesifik yang identik dengan ligan alami reseptor target.

The curcumin analog 3,5-bis(4-methoxybenzylidene)-4-piperidone was synthesised via a Claisen-Schmidt condensation reaction under basic conditions using sonication. The resulting curcumin analog was characterized by ATR-IR, 1H-NMR, and 13C-NMR, and formulated into a nanosuspension using the solvent-evaporation nanoprecipitation method with dichloromethane as the solvent and Tween 60 as a stabilizer. The curcumin analogs and their nanosuspensions were evaluated pharmacokinetically via particle stability testing using PSA-DLS and pharmacodynamically via molecular docking to the proteins ER?, Bcl-2, and PI3K. The synthesized curcumin analogs and nanosuspension formulations were evaluated as candidate chemopreventive agents for breast cancer in MCF-7 cells. The synthesis of curcumin analog compounds yielded an 84.7% yield with 91.6% purity. The curcumin analog nanosuspension formulation had an average particle size of 116 nm, a polydispersity index of 0.3, and a zeta potential of ?52.1 mV. The curcumin analog nanosuspension exhibits greater inhibitory activity against MCF-7 cancer cells and higher selectivity compared to the non-nanosuspension curcumin analog formulation. The resulting IC50 values were 15.01 and 33.64 ?g mL-1, with selectivity indices of 20.4 and 1.75, respectively. Curcumin analog nanosuspension formulations exhibit better inhibitory activity than curcumin due to increased solubility and lower affinity for specific amino acid residues identical to the natural ligands of the target receptors.

Kata Kunci : analog kurkumin, nanosuspensi, penambatan molekul, sitotoksisitas