In Silico Study of Mangosteen Fruit (Garcinia mangostana L.) as Pancreatic Anticancer Against AKT Kinase

Angela Alysia Elaine, Akhyatun Nisa, Nabila Tahara, Dzulfah Qurrotul Aini, Zulvan Syahriar

Abstrak


Keganasan pada pankreas diakibatkan karena tidak terkendalinya proliferasi sel yang akan mengarah
pada berkurangnya proses apoptosis sel. Oleh karena itu, salah satu usaha untuk menangani kasus
kanker pankreas ini adalah dengan menghambat protein antiapoptosis seperti AKT kinase. Inhibisi
protein AKT kinase didasarkan pada mekanisme penghambatan fosforilasi protein AKT kinase pada
sel pankreas. Senyawa golongan xanton dari buah manggis (Garcinia mangostana L.) telah terbukti
memiliki aktivitas antikanker. Pada penelitian ini senyawa golongan santon diteliti potensinya sebagai
obat anti kanker pankreas melalui metode penambatan molekuler yang dilakukan terhadap reseptor
protein AKT kinase dengan bantuan AutoDockTools (versi 4,2.6 dan 1.5.6), divisualisasikan dengan
BIOVIA Discovery Studio 2020, lalu analisis profil farmakokinetika serta toksisitas dan drug-likeness
yang mengacu pada Lipinski’s Rule of Five melalui situs web pre-ADMET. Penambatan molekuler
menghasilkan 5 senyawa turunan santon yang memenuhi kriteria. Senyawa 1-isomangostin memiliki
potensi aktivitas yang lebih baik jika dibandingkan dengan ligan pembanding dan ligan uji lainnya
dengan energi ikatan (ΔG) -9,90 kkal/mol dan konstanta inhibisi 54,9 nM. Hasil prediksi ADMET dari
1-isomangostin menunjukkan sifat absorpsi yang baik (HIA = 94%, Caco2 = 39,97), distribusi yang
baik (PPB = 79,1%), tidak mampu menembus sawar otak (BBB = 0,179), dan tidak bersifat toksik.


Kata Kunci


Pancreatic cancer; AKT kinase protein; xanthone compounds; mangosteen; molecular docking.

Teks Lengkap:

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Referensi


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DOI: https://doi.org/10.24198/ijbp.v3i1.42601

DOI (PDF): https://doi.org/10.24198/ijbp.v3i1.42601.g19984

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