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SENYAWA BIOAKTIF DARI DAUN MIANA SEBAGAI KANDIDAT PENGHAMBAT BETA-LAKTAMASE: STUDI KOMPUTASI Oktaviana, Lina; Moulana, Mohammad Zaeni; Rusdin, Agus; Lestari, Mila Ayu; Fathin, Nayla Maymuna; Novitasari, Dhania
Jurnal Insan Farmasi Indonesia Vol 7 No 3 (2024): Jurnal Insan Farmasi Indonesia
Publisher : Sekolah Tinggi Ilmu Kesehatan ISFI Banjarmasin

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.36387/392s0e44

Abstract

Antibiotic resistance occurs through several mechanisms, one of which is  increase in beta-lactamase which can inactivate beta lactam antibiotics. The approach in finding new sources of antibiotics can be done by utilizing natural resources, one of which could be developed is miana leaves (Coleus scutellarioides). However, there has been no evaluation study related the antibacterial potential of the bioactive content  miana leaves against beta-lactam. This study analyzed the potential of bioactive compounds from miana leaves as beta-lactamase inhibitors through a computational approach. The methods used include physicochemical and pharmacokinetic profile prediction analysis, followed by pharmacophore screening and molecular docking. The results showed that most of the bioactive compounds of C. scutellarioides fulfill Lipinski's rule and show a good ADMET profile. Pharmacophore analysis produced the best model with an area under curve (AUC) score of 0.87. Molecular docking studies showed the compound 1-(4-phenylcyclohexyl)-1-hexanone had the highest binding affinity to beta-lactamase with a binding energy of -7.2 kcal/mol. This molecular interaction involves hydrogen bonding with amino acid residue GLU272 and van der Waals interaction toward ALA292 and TYR150. Therefore, bioactive compounds from miana leaves show potential as beta-lactamase inhibitors and open opportunities for the development of new antibacterial therapies based natural resources.
STUDI IN SILICO SENYAWA AKTIF DAUN KEMANGI IMBO (Pycnarrhena cauliflora) TERHADAP RESEPTOR ESTROGEN ALFA (ER⍺) SEBAGAI KANDIDAT ANTIKANKER PAYUDARA Fa’aizah Masayu Kyla; Rahmadhani Nabilah; Masyithah Sitti; Sari Fiona Puspita; Fathin Nayla Maymuna; Rusdin Agus; Novitasari Dhania
Pharmacoscript Vol. 7 No. 2 (2024): Pharmacoscript
Publisher : Lembaga Penelitian dan Pengabdian Masyarakat, Universitas Perjuangan Tasikmalaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.36423/pharmacoscript.v7i2.1762

Abstract

Daun kemangi imbo (Pycnarrhena cauliflora) dikenal memiliki sifat farmakologis, salah satunya berpotensi sebagai agen antikanker payudara. Jenis kanker payudara banyak ditandai dengan adanya ekspresi berlebih pada protein hormon, salah satunya ialah reseptor estrogen alpha (ER⍺). Penelitian ini bertujuan mengkaji senyawa yang terdapat dalam daun kemangi imbo yang berpotensi untuk agen antikanker payudara tertarget pada ER⍺. Pengujian yang dilakukan dengan pendekatan studi komputasi, seperti prediksi Lipinski rule of five, prediksi ADMETOKS, penapisan farmakofor, dan penambatan molekuler. Hasil studi menunjukkan bahwa semua senyawa yang diidentifikasi dari daun kemangi imbo memenuhi persyaratan Lipinski rule of five. Penentuan ADMETOKS pada sepuluh senyawa memiliki persentase human intestinal absorption (HIA) yang baik dan penetrasi blood brain barrier (BBB) yang tinggi, permeabilitas Caco-2 yang sedang, sebagian besar memiliki ikatan protein plasma (PPB) yang tinggi, dan beberapa senyawa diprediksi bersifat mutagen dan karsinogenik. Penapisan farmakofor diperoleh kurva nilai AUC100 sebesar 0,95 dan senyawa yang hit yaitu β-sitronelol dengan fit score 43,00. Pada molecular docking, senyawa longipinocarvone menunjukkan kemiripan paling tinggi dengan native ligand yaitu afimoxifene (4-OHT), dengan energi bebas Gibbs paling negatif (-8,20 kkal/mol) dan konstanta inhibisi paling kecil (0,98 µM). Di antara senyawa metabolit sekunder yang terkandung dalam daun kemangi imbo, longipinocarvone menunjukkan potensi untuk dikembangkan sebagai agen antikanker payudara tertarget pada ER⍺.
STUDI IN SILICO SENYAWA BIOAKTIF DALAM DAUN ZAITUN (Olea europaea L.) SEBAGAI ACE INHIBITOR DALAM HIPERTENSI Rizal Alya Izzati Zhafira; Putri Salma Chiara; Aisyah Tasza Noor; Ardhita Marshella Dhanu; Rusdin Agus; Fathin Nayla Maymuna; Novitasari Dhania
Pharmacoscript Vol. 7 No. 2 (2024): Pharmacoscript
Publisher : Lembaga Penelitian dan Pengabdian Masyarakat, Universitas Perjuangan Tasikmalaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.36423/pharmacoscript.v7i2.1763

Abstract

Daun zaitun (Olea europaea L.) telah diketahui memiliki efek penurunan tekanan darah dengan salah satu mekanismenya ialah mempengaruhi aktivitas angiotensin-converting enzyme (ACE), namun aktivitas molekuler pada enzim tersebut masih belum ditelusuri. Studi ini bertujuan untuk mengevaluasi potensi senyawa metabolit sekunder dari daun zaitun terkait dengan karakteristik fisikokimiawi dan profil ADMET, serta interaksinya terhadap ACE melalui studi komputasi. Berdasarkan Samy et al., 2022, dipilih 10 senyawa daun zaitun yang memenuhi Rule of Five dari beberapa senyawa diteliti serta dievaluasi berdasarkan kaidah Lipinski, profil ADMET, skrining farmakofor, dan penambatan molekul. Berdasarkan hasil studi yang dilakukan, senyawa oleuropein aglikon menunjukkan aktivitas paling potensial terhadap target protein ACE (kode PDB: 3BKL) dengan data nilai ikatan bebas dan konstanta inhibisi paling kecil yaitu -7,73 kkal/mol dan 2,16 µM, serta memiliki interaksi pada residu asam amino HIS A: 513 dan TYR A: 523. Hasil studi ini menambah bukti saintifik terkait pengaruh senyawa bioaktif pada daun zaitun khususnya oleuropein aglikon terhadap protein ACE sehingga berpotensi dalam memberikan efek penurunan tekanan darah.
Rosmarinic Acid from Orthosiphon aristatus Potentially Targets Estrogen Receptor-Alpha in Breast Cancer: In-silico Study Qurrotaayun, Ghina Alya Putri; Sitompul, Joy Elizabeth Nauli; Fadhilah, Naya; Pramudita, Fransisca Widi; Putri, Nazwa Septiriana; Muljono, Fajar Oktavian; Fardhan, Firghi Muhammad; Novitasari, Dhania
Indonesian Journal of Cancer Chemoprevention Vol 15, No 2 (2024)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev15iss2pp150-161

Abstract

Breast cancer is the most common cancer among women. Tamoxifen, a widely used estrogen receptor-alpha (ER-α) inhibitor, is effective but often causes side effects, necessitating the search for alternative inhibitors from natural sources. Ortosiphon aristatus, also known as cat's whiskers, is a medicinal plant traditionally valued for its anti-inflammatory and antioxidant properties. Recent studies suggest its bioactive compounds may exhibit anticancer activity by inducing apoptosis in cancer cell lines. This study explores the potential of O. aristatus metabolites as ER-α inhibitors using computational approaches. Nine metabolites were assessed for their physicochemical properties based on Lipinski’s rule of five and ADMET predictions, followed by pharmacophore-based virtual screening with LigandScout and molecular docking with AutoDock. The results showed that all tested compounds complied with Lipinski’s rule, and most met ADMET criteria. Among these, rosmarinic acid was identified as one of the hit compounds based on pharmacophore screening, exhibiting binding interactions comparable to 4-hydroxytamoxifen with the ER-α amino acid residues HIS524 and GLY521. It also demonstrated a binding energy of -8.02 kcal/mol and a low inhibition constant (Ki) of 1.31 μM. These findings highlight the potential of O. aristatus and rosmarinic acid for further evaluation as candidates against ER-α in breast cancer cells.Keywords: breast cancer, estrogen receptor-alpha, Orthosiphon aristatus, in silico.
Confirmation of the potential mechanism of pentagamavunon-0 against temporomandibular arthritis using bioinformatic approaches Robin, Dwi Merry Christmarini; Ardhani, Retno; Novitasari, Dhania; Kusumawardani, Banun; Aulia Rahman, Faaza; Meiyanto, Edy; Purwanti, Nunuk
Dental Journal (Majalah Kedokteran Gigi) Vol. 58 No. 4 (2025): December
Publisher : Faculty of Dental Medicine, Universitas Airlangga https://fkg.unair.ac.id/en

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/j.djmkg.v58.i4.p367-375

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAID) are widely used in temporomandibular joint osteoarthritis management. However, the side effects of NSAIDs on multiple organs need to be anticipated. Curcumin is known for its anti-inflammatory and analgesic potential, comparable to that of NSAIDs. In a previous study, structurally modified curcumin increased the pharmacological effect and simultaneously reduced the toxicity and side effects of curcumin. Pentagamavunon-0 (PGV-0) is one of the active components synthesized by the structure modification of curcumin. Purpose: In this study, we identify the potential target of PGV-0 on the pathogenesis of temporomandibular arthritis characterized by inflammation. Methods: We used a bioinformatics approach to compare the PGV-0 target with curcumin and diclofenac sodium as controls. We identified overlapping gene targets of bioactive compounds (PGV-0, curcumin, or diclofenac sodium) retrieved from the SwissTargetPrediction and GeneCards platforms, specifically for temporomandibular arthritis. An interaction model among targets was developed using the STRING database and Gene Ontology Panther to expound on the bioactive compound’s function on the key signaling pathway. Finally, we formulated a molecular docking prediction between the bioactive compound and the target protein marker derived from the previous analysis using Molecular Operating Environment tools. Results: This study found that curcumin and PGV-0 targeted different molecular pathways in temporomandibular arthritis compared to diclofenac sodium. Curcumin and PGV-0 shared a similar pathway to curcumin by modulating metalloproteinases (MMPs), especially MMP-9 and MMP-13. Moreover, diclofenac sodium influenced cyclooxygenase metabolism. Conclusion: In this study, PGV-0 targeted metalloproteinase in temporomandibular arthritis pathogenesis. This finding underlines the PGV-0 advantage in preventing metalloproteinase-related tissue damage in temporomandibular arthritis.
Catechin from Avocado Seed (Persea Americana Mill.) Potentially Targets Estrogen Receptor-Alpha: Computational-Based Analysis Aulia, Martiza; Rosani, Fahrana; Romadhona, Tarisa Nurafni; Kinanti, Lintang Gusti; Gabriel, Kevin; Rusdin, Agus; Novitasari, Dhania
Biota : Jurnal Ilmiah Ilmu-Ilmu Hayati Vol 10, No 3 (2025): October 2025
Publisher : Universitas Atma Jaya Yogyakarta

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24002/biota.v10i3.10666

Abstract

Avocado seeds (Persea americana Mill.) are known to possess various pharmacological properties, including notable anticancer potential. While preliminary studies have reported the cytotoxic effects of avocado seed extracts on breast cancer cells, there is still a lack of comprehensive research exploring the underlying molecular mechanisms responsible for these effects. This study explores bioactive compounds found in avocado seeds as potential agents targeting estrogen receptor alpha (ERα), a key biomarker in breast and cervical cancers. The investigation employs a range of computational approaches, including the Lipinski Rule of Five, ADME/Tox predictions, pharmacophore screening, and molecular docking analysis. Of the ten tested compounds, seven passed the Lipinski Rule of Five. ADME/Tox analysis revealed that most compounds exhibited adequate human intestinal absorption (HIA), poor blood-brain barrier (BBB) penetration, moderate Caco-2 permeability, and good plasma protein binding (PPB), while some were predicted to be mutagenic or carcinogenic. Pharmacophore modeling yielded an AUC of 0.87, with procyanidin B scoring 45.09 as a hit compound. Molecular docking revealed catechin, hyoscyamine, and atropine had the lowest Gibbs free energy (-5.15, -0.10, -0.07 kcal/mol). Among the compounds, catechin in avocado seed shows the highest potential for development as an ER-targeted anticancer agent.
Antimigratory Evaluation from Curcumin-Derived Synthetic Compounds PGV-1 and CCA-1.1 on HCC1954 and MDA-MB-231 Cells Novitasari, Dhania; Meiyanto, Edy; Kato, Jun-ya; Jenie, Riris Istighfari
Indonesian Journal of Cancer Chemoprevention Vol 13, No 2 (2022)
Publisher : Indonesian Society for Cancer Chemoprevention

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.14499/indonesianjcanchemoprev13iss2pp71-82

Abstract

Earlier findings reported the anticancer-mediated activities of curcumin-modified compounds Pentagamavunone-1 (PGV-1) and Chemoprevention Curcumin Analog 1.1 (CCA-1.1) with several mechanisms including cell cycle arrest, reactive oxygen species (ROS) production, and cell migration disruption. Our study aims to evaluate the antimigratory activity of PGV-1 and CCA-1.1 on aggressive breast cancer cell lines (MDA-MB-231 and HCC1954 cells) and their effect on HER2 protein. The trypan blue exclusion method was conducted for the antiproliferative effect. The PGV-1 or CCA-1.1 effect on cell migration was determined by wound healing assay. Using gelatin zymography, we checked the secretion level of matrix metalloproteinase (MMP). We also evaluated the human epidermal growth receptor-2 (HER2) level after incubation with PGV-1 or CCA-1.1 in HCC1954 cells by western blot. Based on the antiproliferation assay, MDA-MB-231 and HCC1954 cells were sensitive to PGV-1 and CCA-1.1. MMP-2 was only observed in HCC1954 cells while MMP-9 was only observed in MDA-MB-231. Both PGV-1 and CCA-1.1 significantly suppressed MMP-9 activity in MDA-MB-231 cells. Moreover, PGV-1 inhibited HER2 protein levels in HCC1954 although it was not significant, whereas CCA-1.1 did not affect HER2 protein. This study strengthens the scientific evidence for PGV-1 and CCA-1.1 activities for future exploration as candidate chemotherapy with multitarget against breast cancer.Keywords: Curcumin analog, cell migration, MMP-9, HER2, breast cancer.
The potency of bioactive constituents in Piper betle L. for Alzheimer Targeting on Caspase-3 - in silico studies Putri, Anindya Calista Nabila; Ashriany, Raissa Rerey; Salsabila, Sitti Kesya; Rahmaharva, Naila Dwi; Muljono, Fajar Oktavian; Fardhan, Firghi Muhammad; Novitasari, Dhania
Journal of Pharmaceuticals and Natural Sciences Vol. 1 No. 2 (2024): J. Pharm. Nat. Sci.
Publisher : B-CRETA Publisher (CV. Borneo Citra Kreatama)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.70392/rw708r52

Abstract

Alzheimer’s disease (AD) is a neurodegenerative condition that can disrupt memory, cognition, and neurological functions, Recent studies highlight caspase-3 as a potential target, with several lines of evidence pointing to the enzyme's possible role in the onset of AD. Several findings revealed that betel leaf was also examined to treat AD by targeting acetylcholinesterase in vitro and in silico, yet no evaluation had not been done in caspase-3 activity. Using molecular docking, Lipinski's and PreADMET prediction, an in-silico analysis of compounds found in betel leaf (Piper betle L.) was conducted in order to determine whether these compounds could be applied as therapeutic candidates in the treatment of Alzheimer's. To ascertain the drug similarity and ADMET profile of the evaluated ligands, the Mcule and PreADMET sites were used in the studies, which were followed by the molecular docking simulation software AutoDock. The findings demonstrated that all the tested compounds passed the physicochemical features based on Lipinski rule. Further analysis then showed that arecoline bound to the critical amino acid that involved in caspase-3 inhibition. Further evaluation needs to be done to confirm the molecular mechanism of P. betle leaves to AD.
Sinensetin pada Biji Pinang (Areca catechu) sebagai kandidat COX-2 Inhibitor pada Osteoarthritis: Studi In Silico Maharani, Anisa; Nurhaliza, Muthiah; Azzahra, Iqlima; Cindy, Cindy; Gabriel, Kevin; Rusdin, Agus; Novitasari, Dhania
Jurnal Farmasi Sains dan Terapan (Journal of Pharmacy Science and Practice) Vol. 12 No. 2 (2025): October
Publisher : Faculty of Pharmacy, Widya Mandala Surabaya Catholic University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33508/jfst.v12i2.5756

Abstract

Osteoarthritis (OA) merupakan penyakit peradangan sendi degeneratif akibat kerusakan tulang rawan yang termasuk ke dalam 10 besar penyakit lansia paling umum di Indonesia. COX-2 inhibitor secara selektif menginhibisi aktivitas enzim COX-2 sehingga menimbulkan efek analgesik dan antiinflamasi yang dapat mengurangi rasa sakit pada pasien osteoarthritis.  Berdasarkan penelitian yang telah ada, ekstrak biji pinang berpotensi menurunkan inflamasi sendi lutut. Tujuan dari penelitian ini adalah untuk menemukan kandungan bioaktif dalam biji pinang (Areca catechu) yang potensial sebagai antiinflamasi dan agen terapi baru pada OA melalui pendekatan komputasi secara in silico dengan molecular docking berdasarkan energi ikatan (∆G), konstanta inhibisi (KI), dan interaksi ikatan. Hasil molecular docking menunjukkan senyawa sinensetin memiliki energi ikatan terbaik yaitu -9,52 kcal/mol dan paling mendekati energi ikatan celecoxib yaitu -11,09 kkal/mol. Adapun konstanta inhibisi senyawa sinensetin yaitu 104,30 μM dan interaksi ikatan dengan reseptor COX-2 menunjukkan adanya interaksi ikatan hidrogen ILE A:503; ikatan karbon-hidrogen SER A:339; ikatan pi-sigma VAL A:509; ikatan alkyl VAL A:335, TRP A:373, LEU A:370; ikatan pi-alkyl VAL A:509. Oleh karena itu, sinensetin pada biji pinang berpotensi untuk dijadikan sebagai kandidat antiinflamasi khususnya untuk terapi osteoarthritis.
Uncovering Anti-Obesity Candidates from Robusta Green Coffee: In Silico Evaluation of Bioactive Compounds Targeting PPAR-α Mahardika, Bintang Satrio; Putri, Viona Algesia Fiola; Putri, Yolla Adellia; Jasimah, Jasimah; Gabriel, Kevin; Rusdin, Agus; Novitasari, Dhania
Journal of Pharmaceuticals and Natural Sciences Vol. 2 No. 3 (2025): J. Pharm. Nat. Sci.
Publisher : B-CRETA Publisher (CV. Borneo Citra Kreatama)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.70392/jpns.v2i3.40

Abstract

Obesity arises from a chronic imbalance between energy intake and expenditure, leading to excessive accumulation of body fat. Peroxisome proliferator-activated receptor-alpha (PPARα) plays a key regulatory role in lipid metabolism, particularly in reducing the de novo synthesis of fatty acids. Robusta coffee has been widely consumed as part of the lifestyle, yet scientific evidence for its pharmacological effects is limited. This study aimed to evaluate the molecular interactions between secondary metabolites from Green Bean Coffee Robusta (Coffea canephora P.) and PPARα using in silico approaches. The workflow included screening compounds from C. canephora based on Lipinski’s Rule of Five (RO5) and ADMET predictions, followed by pharmacophore modelling and molecular docking simulations using AutoDock against PPARα (PDB ID: 2P54). All the bioactive constituents in C. canephora met the requirements of RO5, and several metabolites were assessed based on their pharmacokinetic profile and toxicology prediction. Further molecular docking analysis identified 4-ethyl-2-methoxyphenol as the most promising anti-obesity candidate, demonstrating the lowest binding energy (-4.58 kcal/mol) and an inhibition constant of 440.47 µM. The compound formed key hydrogen bonds with amino acid residues ALA333, THR279, CYS276, and CYS275. These findings suggest that 4-ethyl-2-methoxyphenol from Green Bean Coffee Robusta exhibits potential as an anti-obesity agent through its interaction with the PPARα receptor. Further in vitro and in vivo studies are required to validate its pharmacological effects.
Co-Authors Adam Hermawan Ade Safitri Aisyah Tasza Noor Alifa, Zahra Andhryanti, Rifa Nurfadila Andika Andika Anselma Ivanawati Ardhita Marshella Dhanu Ashriany, Raissa Rerey Aulia Rahman, Faaza Aulia, Martiza Azzahra, Iqlima Banun Kusumawardani Beni Lestari Cahyaningrum, Lydia CINDY CINDY Devyanto Hadi Triutomo Dwi Merry Christmarini Robin Ediati Sasmito Ediati Sasmito Edy Meiyanto Edy Meiyanto Edy Meiyanto Edy Meiyanto Fadhilah, Naya Fardhan, Firghi Muhammad Fathin Nayla Maymuna Fathin, Nayla Maymuna Fa’aizah Masayu Kyla Fitriana Hayyu Arifah Gabriel, Kevin Herwandhani Putri Hess, Aurelina Yunita Ismail, Dzava Prawinsyah Fairus Jasimah, Jasimah Jun-ya Kato Kato, Jun-Ya Kinanti, Lintang Gusti Laeli Muntafiah Lathifah, Salma Sri Layung Sekar Sih Wikanthi Lestari, Mila Ayu Maharani, Anisa Mahardika, Bintang Satrio Mahira, Tsania Masyithah Sitti Moordiani Moordiani Moulana, Mohammad Zaeni Muhammad Syahid Muljono, Fajar Oktavian Muthi Ikawati Nindi Wulandari Nunuk Purwanti Nur Fitra Sari Nurhaliza, Muthiah Oktaviana, Lina Pramudita, Fransisca Widi Prisnu Tirtanirmala Putri Salma Chiara Putri, Anindya Calista Nabila Putri, Nazwa Septiriana Putri, Viona Algesia Fiola Putri, Yolla Adellia Qurrotaayun, Ghina Alya Putri Rahmadhani Nabilah Rahmaharva, Naila Dwi Rahmawati Rahmawati Ramadhani, Siti Zhahira Ratna Asmah Susidarti Retno Ardhani Retno Murwanti Riris Istighfari Jenie Riris Istighfari Jenie Rizal Alya Izzati Zhafira Romadhona, Tarisa Nurafni Rosani, Fahrana Rubianti, Retno Rusdin, Agus Rusmina Aulia Hasanah Salsabila, Sitti Kesya Sari Fiona Puspita Sari Haryanti Shafa, Nafis Sitompul, Joy Elizabeth Nauli Sri Handayani Zahrotul Ulum Zhafirah, Noor