PREDIKSI SENYAWA KUINOLIN SEBAGAI KANDIDAT ANTITUBERKULOSIS MELALUI PENAMBATAN MOLEKULER DAN KAJIAN HKSA

Tuberkulosis masih menjadi penyakit menular yang menyebabkan angka kematian tinggi sampai hari ini. Beberapa negara sedang memikirkan bagaimana cara mengendalikan penyakit yang disebabkan oleh Mycobacterium tuberculosis terlebih lagi TBC yang sudah resisten terhadap obat (TB RO). Penelitian ini bertujuan untuk mengetahui prediksi pola interaksi dari penambatan molekuler untuk mendapatkan nilai yang efektif dan stabil serta desain senyawa baru turunan kuinolin beraktivitas antituberkulosis yang lebih poten berdasarkan model persamaan HKSA yang terbaik dan valid. Penelitian ini menggunakan kumpulan data 22 senyawa turunan kuinolin yang mempunyai MIC terhadap antituberkulosis. Skor penambatan dan nilai deskriptor dari parameter elektronik, hidrofobik, dan sterik dihubungkan menjadi suatu persamaan HKSA terbaik dengan aplikasi BuildQSAR. Persamaan HKSA digunakan sebagai desain senyawa turunan kuinolin yang lebih poten. Hasil penelitian menunjukkan nilai RMSD 1,6582 dan beberapa derivat senyawa memiliki pola interaksi dan afinitas, kesamaan asam amino, serta binding pocket yang baik terhadap target M.tuberculosis. Analisis model persamaan HKSA terbaik diperoleh memenuhi syarat kaidah Hansch yaitu skor docking = - 74.7676 (± 79.8850) qC2 + 29.8560 (± 60.1549) qC5 - 0.0664 (± 0.0181) V - 0.4060 (± 0.5058) u + 0.0189 (± 0.0189) Hf - 27.0100 (± 22.4443) dengan parameter statistik (n = 20; R = 0.973; s = 3.280; F = 49.908; p < 0.0001; Q2 = 0.908; SPress = 4.324; SDEP = 3.712. Desain struktur dibuat berdasarkan persamaan HKSA sehingga diperoleh nilai skor penambatan molekul sebesar -137,544 dan -135,894 yaitu senyawa 4-(5-(acetamidomethyl) 2-oxooxazolidin-3-yl)-8-(trifluoromethyl)quinoline-6-carboxylic acid dan N-((3-(3-iodo-6-methoxy-8-(trifluoromethyl)quinolin-4-yl)-2 oxooxazolidin-5-yl)methyl)acetamide. Tuberculosis is still an infectious disease that causes high mortality rates to this day. Some countries are thinking about how to control the disease caused by Mycobacterium tuberculosis, especially drug-resistant tuberculosis (RO TB). This study aims to determine the prediction of interaction patterns from molecular tethering to obtain effective and stable values and the design of new compounds derived from quinolins with more potent antituberculosis activity based on the best and valid QSAR equation model. This study used a data set of 22 quinolin-derived compounds that have MIC against antituberculosis. Tether scores and descriptor values of electronic, hydrophobic, and steric parameters are linked into the best QSAR equation with the BuildQSAR application. The QSAR equation is used as a design of more potent quinolin-derived compounds. The results showed an RMSD value of 1.6582 and several compound derivatives had interaction patterns and affinities, amino acid similarities, and good pocket binding against M. tuberculosis targets. The best QSAR equation model analysis was obtained to meet the requirements of Hansch's rule, namely docking score = - 74.7676 (± 79.8850) qC2 + 29.8560 (± 60.1549) qC5 - 0.0664 (± 0.0181) V - 0.4060 (± 0.5058) u + 0.0189 (± 0.0189) Hf - 27.0100 (± 22.4443) with statistical parameters (n = 20; R = 0.973; s = 3.280; F = 49.908; p < 0.0001; Q2 = 0.908; SPress = 4,324; SDEP = 3,712. The structural design was made based on the QSAR equation so that molecular tethering scores of -137.544 and -135.894 were obtained 4-(5 (acetamidomethyl)-2-oxooxazolidin-3-yl)-8-(trifluoromethyl)quinoline 6-carboxylic acid and N-(3-(3-iodo-6-methoxy-8 (trifluoromethyl)quinolin-4-yl)-2-oxooxazolidin-5 yl)methyl)acetamide.