Sintesis Turunan N-fenilpirazolina Berbahan Dasar 2-Asetil-5-klorotiofena serta Uji Aktivitasnya sebagai Antikanker

Nikma Farismatur Riza, Prof. Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D.; Dr. Endang Astuti, M.Si.

2025 | Tesis | S2 Ilmu Kimia

Sintesis turunan N-fenilpirazolina P1-P8 dari bahan dasar 2-asetil-5-klorotiofena telah dilakukan melalui dua tahapan reaksi yang melibatkan intermediet kalkon, diikuti dengan evaluasi bioaktivitasnya sebagai kandidat agen antikanker. Pada tahap pertama, kalkon K1-K8 disintesis melalui reaksi kondensasi Claisen-Schmidt dengan mereaksikan 2-asetil-5-klorotiofena dan beberapa turunan benzaldehida yaitu: 2-metoksibenzaldehida, 3-metoksibenzaldehida, 2,4-dimetoksibenzaldehida, 2,5-dimetoksibenzaldehida, 2,3,4-trimetoksibenzaldehida, 3,4,5-trimetoksibenzaldehida, piperonal, dan DMAB. Reaksi dilakukan dengan metode pengadukan menggunakan katalis basa. Selanjutnya, N-fenilpirazolina disintesis melalui reaksi siklokondensasi menggunakan metode refluks antara kalkon dengan fenilhidrazina menggunakan NaOH sebagai katalis. Elusidasi struktur dilakukan dengan instrumentasi IR, GC-MS, 1H- dan 13C-NMR. Pengujian aktivitas antikanker dilakukan pada senyawa N-fenilpirazolina terhadap sel kanker HeLa, T47D, MCF-7, WiDr, serta sel normal Vero dengan metode MTT.

Sintesis senyawa N-fenilpirazolina P1-P8 menghasilkan padatan dengan persen hasil berkisar antara 58,78–94,50%. Uji aktivitas antikanker menunjukkan bahwa di antara seri senyawa pirazolina yang diuji, senyawa P7, yaitu turunan pirazolina berbasis klorotiofena yang mengandung gugus benzo[1,3]dioksol, menunjukkan aktivitas sitotoksik paling baik terhadap sel kanker kolorektal WiDr, dengan nilai IC50 sebesar 19,63 ?g/mL, serta menunjukkan indeks selektivitas (IS) tertinggi yaitu sebesar 665,88.

A series of N-phenylpyrazoline derivatives P1-P8 was successfully synthesized from 2-acetyl-5-chlorothiophene through a two-step reaction pathway involving chalcone intermediates, followed by an evaluation of their bioactivity as an anticancer compound. In the first step, chalcones K1–K8 were prepared via Claisen–Schmidt condensation between 2-acetyl-5-chlorothiophene and various benzaldehyde derivatives, i.e., 2-methoxybenzaldehyde, 3-methoxybenzaldehyde, 2,4-dimethoxybenzaldehyde, 2,5-dimethoxybenzaldehyde, 2,3,4-trimethoxybenzaldehyde, 3,4,5-trimethoxybenzaldehyde, piperonal, and DMAB. The reactions were carried out using stirring method with base catalyst. Subsequently, N-phenylpyrazolines were synthesized through cyclocondensation reaction by refluxing chalcones with phenylhydrazine in the presence of NaOH as a catalyst. Structure elucidation was performed using IR, GC-MS, 1H- and 13C-NMR. The anticancer activity of the synthesized N-phenylpyrazolines were assessed against HeLa, T47D, MCF-7, and WiDr cancer cell lines, as well as normal Vero cells, using the MTT assay.

The synthesis of N-phenylpyrazoline derivatives P1–P8 yielded solid compounds with yields ranging from 58.78–94.50%. Among the tested compounds, P7, a chlorothiophene-based pyrazoline derivative bearing a benzo[1,3]dioxole moiety, exhibited the most potent cytotoxicity against WiDr colorectal cancer cells, with an IC?? value of 19.63 ?g/mL, and demonstrated the highest selectivity index (SI = 665.88).

Kata Kunci : 2-asetil-5-klorotiofena, antikanker, kalkon, N-fenilpirazolina