ADMET Analysis of Allicin, Capsaicin, Curcumin, and Genistein Compounds as Cancer Drug Candidates
Abstract
Background. Cancer treatment with hormone therapy such as Doxorubicin has been widely practised in breast cancer, bowel cancer, and others. However, sometimes the side effects of hormone therapy appear and worsen the patient's condition. The compounds (test compounds) Allicin, Capsaicin, Curcumin and Genistein have potential as anticancer compounds. The similarity of the medicinal properties of the test compounds with Doxorubicin, allows them to be used as cancer drug candidates. In addition, it is necessary to analyse ADMET to determine the efficacy and safety of the test compounds.
Purpose. This study aims to analyse the ADMET of the compounds Allicin, Capsaicin, Curcumin and Genistein.
Method. This research uses the in silico method. Test compounds; Allicin (PubCHem CID 65036), Capsaicin (PubChem CID 1548943), Curcumin (PubChem CID 969516), Genistein (PubChem CID 5280961) and Doxorubicin (PubChem CID 31703) as positive controls were obtained from PubChem. Analysis of test compounds using the PASS online programme to determine the binding activity of compounds with proteins. To determine absorption, distribution, metabolism, excretion, and toxicity (ADMET) using pkCSM online. DruLiTo was used to analyse the physico-chemical properties of the test compounds.
Results. Allicin has good ADMET with Intestinal absorption 96.229 (%absorbed), BBB permeability 0.506 (log BB), Total Clearance 0.704 (log ml/min/kg), and does not cause hepatotoxicity.
Conclusion. It can be concluded that all test compounds have their own advantages and disadvantages, but Allicin has better ADMET than other test compounds. Further research on Molecular Dynamics needs to be done to find out the interaction of test compounds with Caspase-3 Protein.
Full text article
References
Ab, Kunnumakkara, Bordoloi D, Padmavathi G, Monisha J, Roy Nk, Prasad S, and Aggarwal Bb. 2017. ‘Curcumin, the Golden Nutraceutical: Multitargeting for Multiple Chronic Diseases’. British Journal of Pharmacology 174(11). doi: 10.1111/bph.13621.
Adrain, C., and S. J. Martin. 2001. ‘The Mitochondrial Apoptosome: A Killer Unleashed by the Cytochrome Seas’. Trends in Biochemical Sciences 26(6):390–97. doi: 10.1016/s0968-0004(01)01844-8.
Ajai, Gupta, Pandotra Pankaj, Sharma Rajni, and Kushwaha Manoj. 2013. ‘Marine Resource: A Promising Future for Anticancer Drugs’. Stud. Nat. Prod. Chem 40:229–35. doi: 10.1016/b978-0-444-59603-1.00008-4.
Alhasan, S. A., O. Aranha, and F. H. Sarkar. 2001. ‘Genistein Elicits Pleiotropic Molecular Effects on Head and Neck Cancer Cells’. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 7(12):4174–81.
Amantini, Consuelo, Patrizia Ballarini, Sara Caprodossi, Massimo Nabissi, Maria Beatrice Morelli, Roberta Lucciarini, Marco Andrea Cardarelli, Gabriele Mammana, and Giorgio Santoni. 2009. ‘Triggering of Transient Receptor Potential Vanilloid Type 1 (TRPV1) by Capsaicin Induces Fas/CD95-Mediated Apoptosis of Urothelial Cancer Cells in an ATM-Dependent Manner’. Carcinogenesis 30(8):1320–29. doi: 10.1093/carcin/bgp138.
Anand, Preetha, Chitra Sundaram, Sonia Jhurani, Ajaikumar B. Kunnumakkara, and Bharat B. Aggarwal. 2008. ‘Curcumin and Cancer: An “Old-Age” Disease with an “Age-Old” Solution’. Cancer Letters 267(1):133–64. doi: 10.1016/j.canlet.2008.03.025.
Andhiarto, Yanu, Suciati Suciati, Ersanda Nurma Praditapuspa, and Sukardiman Sukardiman. 2023. ‘In Silico Analysis and ADMET Prediction of Flavonoid Compounds from Syzigium Cumini Var. Album on ?-Glucosidase Receptor for Searching Anti-Diabetic Drug Candidates’. Pharmacognosy Journal 14(6):736–43. doi: 10.5530/pj.2022.14.161.
Bratton, S. B., M. MacFarlane, K. Cain, and G. M. Cohen. 2000. ‘Protein Complexes Activate Distinct Caspase Cascades in Death Receptor and Stress-Induced Apoptosis’. Experimental Cell Research 256(1):27–33. doi: 10.1006/excr.2000.4835.
Chelliah, D. Abiya. 2008. ‘Biological Activity Prediction of an Ethno Medicinal Plant Cinnamomum Camphora through Bio-Informatics’. Ethnobot Leafl 12:181–90.
Hou, Shenglin. 2022. ‘Genistein: Therapeutic and Preventive Effects, Mechanisms, and Clinical Application in Digestive Tract Tumor’ edited by G. Cohen. Evidence-Based Complementary and Alternative Medicine 2022:1–10. doi: 10.1155/2022/5957378.
Huang, Weifeng, Chunpeng Wan, Qicong Luo, Zhengjie Huang, and Qi Luo. 2014. ‘Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer’. International Journal of Molecular Sciences 15(3):3432–43. doi: 10.3390/ijms15033432.
Jadhav, PB, Akshay R. Yadav, and Megha G. Core. 2015. ‘Concept of Drug Likeness in Pharmaceutical Research’. Int J Pharm Biol Sci 6:142–54.
Johnson-Arbor, Kelly, and Ramin Dubey. 2024. ‘Doxorubicin’. in StatPearls. Treasure Island (FL): StatPearls Publishing.
Kim, Min Young, Laura J. Trudel, and Gerald N. Wogan. 2009. ‘Apoptosis Induced by Capsaicin and Resveratrol in Colon Carcinoma Cells Requires Nitric Oxide Production and Caspase Activation’. Anticancer Research 29(10):3733–40.
Koleini, Navid, Barbara E. Nickel, Andrea L. Edel, Robert R. Fandrich, Amir Ravandi, and Elissavet Kardami. 2019. ‘Oxidized Phospholipids in Doxorubicin-Induced Cardiotoxicity’. Chemico-Biological Interactions 303:35–39. doi: 10.1016/j.cbi.2019.01.032.
Lavorgna, Margherita, Elena Orlo, Roberta Nugnes, Concetta Piscitelli, Chiara Russo, and Marina Isidori. 2019. ‘Capsaicin in Hot Chili Peppers: In Vitro Evaluation of Its Antiradical, Antiproliferative and Apoptotic Activities’. Plant Foods for Human Nutrition 74(2):164–70. doi: 10.1007/s11130-019-00722-0.
M, Tantari, Barra F, Di Domenico S, Ferraioli D, Vellone Vg, De Cian F, and Ferrero S. 2019. ‘Current State of the Art and Emerging Pharmacotherapy for Uterine Leiomyosarcomas’. Expert Opinion on Pharmacotherapy 20(6). doi: 10.1080/14656566.2019.1571042.
Marcq, Gautier, Edouard Jarry, Idir Ouzaid, Jean-François Hermieu, François Henon, Jean-Christophe Fantoni, and Evanguelos Xylinas. 2019. ‘Contemporary Best Practice in the Use of Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer’. Therapeutic Advances in Urology 11:1756287218823678. doi: 10.1177/1756287218823678.
Özkan, ?rem, Polen Koçak, Merve Y?ld?r?m, Naz Ünsal, Hazal Y?lmaz, Dilek Telci, and Fikrettin ?ahin. 2021. ‘Garlic (Allium Sativum)-Derived SEVs Inhibit Cancer Cell Proliferation and Induce Caspase Mediated Apoptosis’. Scientific Reports 11(1):14773. doi: 10.1038/s41598-021-93876-4.
Pires, Douglas E. V., Tom L. Blundell, and David B. Ascher. 2015. ‘PkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures’. Journal of Medicinal Chemistry 58(9):4066–72. doi: 10.1021/acs.jmedchem.5b00104.
Prakobwong, Suksanti, Subash C. Gupta, Ji Hye Kim, Bokyung Sung, Porntip Pinlaor, Yusuke Hiraku, Sopit Wongkham, Banchob Sripa, Somchai Pinlaor, and Bharat B. Aggarwal. 2011. ‘Curcumin Suppresses Proliferation and Induces Apoptosis in Human Biliary Cancer Cells through Modulation of Multiple Cell Signaling Pathways’. Carcinogenesis 32(9):1372–80. doi: 10.1093/carcin/bgr032.
Siegel, Rebecca L., Kimberly D. Miller, and Ahmedin Jemal. 2018. ‘Cancer Statistics, 2018’. CA: A Cancer Journal for Clinicians 68(1):7–30. doi: 10.3322/caac.21442.
Talib, Wamidh H., Sally Atawneh, Areen Nabil Shakhatreh, Ghyda’a Nabil Shakhatreh, Islam Subhi Rasheed Aljarrah, Reem Ali Hamed, Doaa Adel Banyyounes, and Intisar Hadi Al-Yasari. 2024. ‘Anticancer Potential of Garlic Bioactive Constituents: Allicin, Z-Ajoene, and Organosulfur Compounds’. Pharmacia 71:1–23. doi: 10.3897/pharmacia.71.e114556.
?igu, Adrian Bogdan, Cristian Silviu Moldovan, Vlad-Alexandru Toma, Anca Daniela Farca?, Augustin C?t?lin Mo?, Ancu?a Jurj, Eva Fischer-Fodor, Cristina Mircea, and Marcel Pârvu. 2021. ‘Phytochemical Analysis and In Vitro Effects of Allium Fistulosum L. and Allium Sativum L. Extracts on Human Normal and Tumor Cell Lines: A Comparative Study’. Molecules 26(3):574. doi: 10.3390/molecules26030574.
Umar, Asad, Barbara K. Dunn, and Peter Greenwald. 2012. ‘Future Directions in Cancer Prevention’. Nature Reviews Cancer 12(12):835–48. doi: 10.1038/nrc3397.
Varinska, Lenka, Peter Gal, Gabriela Mojzisova, Ladislav Mirossay, and Jan Mojzis. 2015. ‘Soy and Breast Cancer: Focus on Angiogenesis’. International Journal of Molecular Sciences 16(5):11728–49. doi: 10.3390/ijms160511728.
Yu, Anthony F., Angel T. Chan, and Richard M. Steingart. 2019. ‘Cardiac Magnetic Resonance and Cardio-Oncology: Does T2 Signal the End of Anthracycline Cardiotoxicity?’ Journal of the American College of Cardiology 73(7):792–94. doi: 10.1016/j.jacc.2018.11.045.
Authors
Copyright (c) 2026 Novyananda Salmasfattah, Fendy Prasetyawan, Yuneka Saristiana
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
