Hubungan Kuantitatif Struktur-Aktivitas dan Desain Senyawa Novel PhenylBenzimidazoles sebagai Penghambat Wnt/β-Catenin untuk Terapi PancreaticDuctal Adenocarcinoma

Quantitative Structure-Activity Relationship and Design of Novel PhenylBenzimidazoles as Wnt/β-Catenin Inhibitors for Pancreatic DuctalAdenocarcinoma Therapy

Penulis

  • Dwi Syah Fitra Ramadhan Program Studi Farmasi, Poltekkes Kemenkes Makassar, Makassar, Sulawesi Selatan, Indonesia Penulis
  • Rusli Program Studi Farmasi, Poltekkes Kemenkes Makassar, Makassar, Sulawesi Selatan, Indonesia Penulis
  • Taufik Muhammad Fakih Fakultas MIPA, Universitas Islam Bandung, Bandung, Jawa Barat, Indonesia Penulis

Kata Kunci:

Benzimidazoles, PDAC, HKSA, Wnt/β-Catenin

Abstrak

Jalur pensinyalan Wnt/?-Catenin sangat penting dalam inisiasi dan perkembangan dari pancreatic ductal adenocarcinoma (PDAC). Studi sebelumnya menunjukkan bahwa fenil benzimidazol baru memiliki aktivitas penghambatan di jalur Wnt/?-Catenin. Tujuan dari penelitian ini adalah untuk merancang fenil benzimidazol baru sebagai penghambat Wnt/?Catenin pada PDAC berdasarkan metode Hubungan Kuantitatif Struktur-Aktivitas (HKSA). Struktur molekul dibangun dan dioptimalkan dengan metode AM1 semi empiris menggunakan Gaussian. Sebanyak 12 Deskriptor dipilih yang mewakili parameter elektronik, hidrofobik, dan sterik menggunakan MOE 2014.0901. Senyawa-senyawa yang diduga outlier kemudian dikeluarkan dari kumpulan data berdasarkan nilai XZ-score, yaitu senyawa-senyawa dengan XZ-score di atas 2,5. Kumpulan data kemudian diklasifikasikan menjadi dua bagian, yaitu training set dan test set. Validasi dilakukan menggunakan metode statistik Leave One Out (LOO). Turunan baru dirancang menggunakan skema topliss, dimana senyawa induk dengan nilai IC terendah digunakan sebagai template. Analisis statistik menunjukkan bahwa ada dua deskriptor paling berpengaruh dari aktivitas penghambatan Wnt/?-Catenin: mr dan LogS. Validasi LOO menunjukkan niali Q2 = 0,7363. Enam turunan baru, diprediksi memiliki IC yang lebih rendah dari senyawa induknya.

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Unduhan

Diterbitkan

2023-10-30

Terbitan

Vol 5 No 5 (2023): J. Sains Kes.

Bagian

Articles

Cara Mengutip

Hubungan Kuantitatif Struktur-Aktivitas dan Desain Senyawa Novel PhenylBenzimidazoles sebagai Penghambat Wnt/β-Catenin untuk Terapi PancreaticDuctal Adenocarcinoma: Quantitative Structure-Activity Relationship and Design of Novel PhenylBenzimidazoles as Wnt/β-Catenin Inhibitors for Pancreatic DuctalAdenocarcinoma Therapy. (2023). Jurnal Sains Dan Kesehatan, 5(5), 584-590. https://jsk.ff.unmul.ac.id/index.php/JSK/article/view/438