Hubungan Kuantitatif Struktur-Aktifitas  dan Doking Molekular Senyawa Meso-Tetraphenylporphyrin dan Meso-Tetraphenylchlorin sebagai Fotosensitizer untuk Terapi Fotodinamik

Asmiyenti Djaliasrin Djalil; Nurul Fadhilah Deni Saputri; Suparman Suparman; Alwani Hamad

doi:10.20527/jps.v3i1.5831

Hubungan Kuantitatif Struktur-Aktifitas dan Doking Molekular Senyawa Meso-Tetraphenylporphyrin dan Meso-Tetraphenylchlorin sebagai Fotosensitizer untuk Terapi Fotodinamik

Asmiyenti Djaliasrin Djalil, Nurul Fadhilah Deni Saputri, Suparman Suparman, Alwani Hamad

Abstract

ABSTRAK

Terapi fotodinamik (Photodynamic Therapy/PDT) merupakan metode alternatif pengobatan kanker yang selektif. Terapi ini memerlukan fotosensitizer yang diberi penyinaran dalam lingkungan oksigen sehingga dihasilkan oksigen singlet yang mampu menghancurkan sel kanker dan merusak jaringan. Meso-tetraphenylchlorin (MTPP) dan meso-tetraphenylporphyrin (MTPC) adalah fotosensitizer yang memiliki struktur molekul yang mirip, hanya berbeda kejenuhan pada satu cincin pirolnya. MTPP adalah tetrapirol makrosiklik dengan cincin pirol tidak tereduksi sedangkan struktur MTPC tereduksi pada salah satu cincin pirolnya. Penelitian ini bertujuan untuk memprediksi hubungan antara struktur tetrapirol makrosiklik terhadap aktivitasnya secara in silico. Analisis hubungan kuantitatif-struktur aktifitas (HKSA) menggunakan serangkaian senyawa turunan porfirin dilakukan untuk memperoleh persamaan yang secara statistik memiliki kemampuan korelatif dan prediktif. Perangkat lunak Molecular Operating Environment (MOE) digunakan untuk melakukan analisis HKSA. Doking molekul dilakukan terhadap human serum albumine (HSA) dan peripheral benzodiazepine receptor (PBR) untuk memperoleh energi doking yang berhubungan dengan energi afinitas antara ligan dan reseptor. Simulasi doking dilakukan dengan menggunakan perangkat lunak AutoDock. Hasil menunjukkan bahwa MTPC memiliki energi doking terhadap HSA dan PBR yang paling baik. Analisis HKSA yang diperoleh menunjukkan bahwa MTPC lebih potensial sebagai fotosensitizer yang ditunjukkan dengan nilai IC₅₀ yang lebih kecil.

Kata kunci: doking molekular, fotosensitizer, HKSA, MTPC, MTPP, PDT

ABSTRACT

Photodynamic Therapy (PDT) is an alternative cancer treatment method that can exert a selective cytotoxic activity toward malignant cells. PDT requires a sensitizing agents and light energy, which, in the presence of oxygen, leads to the generation of singlet molecular oxygen in cell. Singlet oxygen molecules are able to kill or inhibit growth of cancer cells. Meso-tetraphenylchlorin (MTPC), a photosensitizer, is similar to meso-tetraphenylporphyrin (MTPP) but the structure has one reduced pyrrole ring. The present study aimed to develop an in silico prediction model that considers PDT activity. The Quantitative-Structure Activity Relationship (QSAR) analysis using a series of porphyrin derivatives was carried out to build a statistically significant model possessing a good correlative and predictive capability for photosensitizer in PDT. Molecular Operating Environment (MOE) software was used to performed the QSAR analysis. Docking molecule of MTPP and MTPC on human serum albumine (HSA) and peripheral benzodiazepine receptor (PBR) had been done to test the docking energy associated with binding affinity between ligand and receptor. Docking simulation was performed by AutoDock software. The results showed that MTPC had the best docking energy to HSA and PBR. Furthermore, the QSAR analysis showed that MTPC had lower IC₅₀ value compare with MTPP. Based on QSAR and molecular docking analysis, MTPC exhibit better photosensitizer as compare with MTPP.

Keywords: molecular docking, photosensitizers, QSAR, MTPC, MTPP, PDT.

Keywords

molecular docking, photosensitizers, QSAR, MTPC, MTPP, PDT

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DOI: http://dx.doi.org/10.20527/jps.v3i1.5831