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"Prevalensi kanker payudara pada tahun 2020 menduduki peringkat pertama di dunia maupun di Indonesia. Pencarian obat antikanker menggunakan metode komputasi dinilai lebih efektif dan selektif. Asam galat dan turunannya (ester dan amida) merupakan senyawa yang memiliki aktivitas biologis seperti antikanker. Tujuan dari studi ini adalah melakukan analisis secara in-siliko dan in-vitro terhadap senyawa turunan asam galat (N-Alkil galamida) sebagai agen apoptosis sel kanker payudara MCF7. Sebelas senyawa N-Alkil galamida yang telah disintesis dilakukan studi in-siliko meliputi, interaksi protein-protein, interaksi obat-protein, analisis ADMET dan pemodelan molekuler. Tiga senyawa terbaik berdasarkan studi in-siliko diuji aktivitas sitotoksisitasnya pada sel MCF7 menggunakan metode MTT dan analisis apoptosis menggunakan annexin V-FITC/PI dengan flow cytometry. Protein target terpilih, yaitu JUN, AKT1, CASP3 dan CASP7. Senyawa N-Oktil galamida, N-Ters-Butil galamida dan N-Isoamil galamida merupakan tiga senyawa terbaik. Senyawa asam galat dan turunannya, secara analisis prediksi ADMET termasuk dalam kategori aman sebagai kandidat obat. Aktivitas sitotoksik ketiga senyawa tersebut dinyatakan dengan nilai IC50 berturut-turut adalah 205.2 ± 0,44 μM, 372.6 ± 4,09 μM, dan 441.7 ± 1,41 μM. Aktivitas apoptosis mencapai 55 hingga 56% dibandingkan dengan kontrol sel. Senyawa N-Oktil galamida, N-Ters-Butil galamida dan N-Isoamil galamida berpotensi sebagai agen apoptosis pada sel kanker payudara MCF7.......The prevalence of breast cancer in 2020 is ranked first in the world and in Indonesia. Searching for anticancer drugs using computational methods is considered more effective and selective. Gallic acid and its derivatives (esters and amides) are compounds that have biological activities such as anticancer. In this study, N-Alkyl gallamides were analyzed in-vitro and in-silico for their potential to act as apoptotic agents for MCF7 breast cancer cells. In-silico investigations on eleven N-alkyl gallamide compounds, including protein-protein interactions, drug-protein interactions, ADMET analysis, and molecular modelling, have been conducted. The three best compounds based on in-silico studies were tested for cytotoxicity activity on MCF7 cells using the MTT assay and apoptosis analysis using annexin V-FITC/PI with flow cytometry. Selected target proteins, namely JUN, AKT1, CASP3 and CASP7. According to ADMET study, gallic acid and their derivatives are safe as therapeutic candidates. The cytotoxic activities of the three compounds were expressed by IC50 values of 205.2 ± 0.44 μM, 372.6 ± 4.09 μM, and 441.7 ± 1.41 μM, respectively. Apoptotic activity reached 55 to 56% compared to control cells. The N-Octyl gallamide, N-Ters-Butyl gallamide and N-Isoamil gallamide compounds have the potential as apoptotic agents in MCF7 cells."

"ABSTRACT

Histone Deacetylase (HDAC) enzymes in the human body play an important role in the transcriptional regulation of gene expression. In the last decade, HDAC inhibitors and activators have been explored and have become known as therapeutic agents for many diseases such as osteodystrophy, neurogenerative disorders, cardiomyopathy, cancer, and diabetes. In recent years, the development of HDAC inhibitors or activators to obtain new potent lead compounds has been conducted using in vitro, in vivo, and in silico methods. Some HDAC family inhibitors and activators have been discovered. But some compounds have limitations such as not selectively binding to one of the HDAC variants. Methods: At present, through bioinformation, HDAC family sequences have been revealed, and some in silico methods such as molecular modelling (homology modelling and pharmacophore modelling), virtual screening, and molecular dynamics are widely used to find and develop new potent and selective compounds. Results: The main utilization of molecular modelling in this work is intended to complete the HDAC structure that partially lacks data regarding its amino acid monomer. Virtual screening methods are helpful in finding the best binding affinity of the test compounds. By molecular dynamic simulation, the temperature, time, and pressure can be adjusted to analyze the hydrogen bond. Conclusion: Combining these in silico approaches will be a more effective and efficient solution in finding new lead compounds for HDAC drug discovery research in the future."