SINTESIS TURUNAN N-BENZOTHIAZOLE PIRAZOLINA DARI 2-ASETIL-5-KLOROTIOFENA DAN UJI AKTIVITASNYA SEBAGAI SENYAWA ANTIKANKER DAN KEMOFLUOROSENSOR

Bhagavad Gita, Prof. Dra. Tutik Dwi Wahyuningsih, M.Si., Ph.D. ; Dr. Deni Pranowo, S.Si., M.Si.

2025 | Tesis | S2 Ilmu Kimia

Sintesis turunan pirazolina berbasis N-benzotiazol dari 2-asetil-5-klorotiofena berhasil dilakukan melalui dua tahap reaksi. Tahap pertama yaitu kondensasi Claisen–Schmidt dengan berbagai turunan benzaldehida menggunakan  NaOH 40% untuk menghasilkan kalkon K1–K8, selanjutnya reaksi siklisasi kalkon dengan 2-hidrazinolbenzotiazol dan NaOH 40% menghasilkan pirazolina P1–P8. Semua kalkon K1-K8 dan pirazolina P1-P8 dikarakterisasi menggunakan FTIR, GC-MS, ¹H- dan ¹³C-NMR. Aktivitas antikanker semua kalkon dan pirazolina dievaluasi secara in vitro menggunakan metode MTT terhadap sel HeLa, T47D, MCF7, WiDr dan Vero, sedangkan kemampuan kemofluorosensor pirazolina P1-P8 dilakukan melalui proses skrining kation, penentuan LoD, LoQ, binding constant dan uji interferensi.

Kalkon K1-K8 diperoleh sebagai padatan dengan persen hasil berkisar 47–97%, sedangkan pirazolina P1-P8 dihasilkan dengan persen hasil berkisar 47–95%. Uji antikanker menunjukkan bahwa semua kalkon berikut memiliki indeks selektivitas yang tinggi yaitu kalkon K1 aktif terhadap sel T47D (IC₅₀ = 1,43 ?g/mL) dan sel WiDr (IC₅₀ = 1,60 ?g/mL), K2 aktif terhadap sel MCF-7 (IC₅₀ = 2,26 ?g/mL), K7 aktif terhadap sel T47D (IC₅₀ 4,96 ?g/mL) dan K8 aktif terhadap sel MCF7 (IC₅₀ 1,08 ?g/mL), sedangkan pirazolina P1-P8 bersifat tidak aktif sebagai antikanker. Uji kemosensor fluoresensi  menunjukkan bahwa pirazolina P3 memiliki respon turn-off yang sangat selektif terhadap ion Hg²? dengan nilai LoD 1,91 µM dan LoQ 6,35 µM serta interferensi minimal. 

The synthesis of N-benzothiazole-based pyrazoline derivatives from 2-acetyl-5-chlorothiophene was successfully carried out through two reaction steps. The first step was the Claisen–Schmidt condensation with various benzaldehyde derivatives using 40% NaOH to yield chalcones K1–K8, followed by cyclization reaction of chalcones with 2-hydrazinobenzothiazole and 40% NaOH to produce pyrazolines P1–P8. All chalcones and pyrazolines were characterized using FTIR, GC-MS, ¹H- and ¹³C-NMR. The anticancer activity of all chalcones and pyrazolines was evaluated in vitro using the MTT method against HeLa, T47D, MCF7, WiDr, and Vero cells, while the chemofluorescent ability of pyrazolines P1-P8 was carried out through a cation screening process, determination of LoD, LoQ, binding constant, and interference test.

 Chalcones K1-K8 were obtained as solids with yields ranging from 47–97%, while pyrazolines P1-P8 were produced with yields ranging from 47–95%. Anticancer tests showed that all of the following chalcones had high selectivity indices, namely chalcone K1 was active against T47D cells (IC₅₀ = 1.43 ?g/mL) and WiDr cells (IC₅₀ = 1.60 ?g/mL), K2 was active against MCF-7 cells (IC₅₀ = 2.26 ?g/mL), K7 was active against T47D cells (IC₅₀ 4.96 ?g/mL) and K8 was active against MCF7 cells (IC₅₀ 1.08 ?g/mL), while pyrazolines P1-P8 were inactive as anticancer agents. Fluorescence chemosensor testing showed that pyrazoline P3 has a highly selective turn-off response to Hg²? ions with a LoD of 1,91 µM and a LoQ of 6,35 µM, along with minimal interference.

Kata Kunci : benzotiazol, kalkon, kemofluorosensor, pirazolina,