Cytotoxic and Computational Profiling of 20 Indole Alkaloids Across Five Breast Cancer Cell Lines
Keywords:
indole alkaloids; breast cancer; apoptosis; Bcl-2; Caspase-3; CDK4; NF-κB; MMP-9; cytotoxicity; molecular docking; ADMET.
Abstract
Indole alkaloids are a structurally diverse class of natural compounds known for their potent anticancer properties, including the ability to induce apoptosis and inhibit cell proliferation and metastasis. This study aimed to evaluate the cytotoxic potential of 20 indole alkaloids against breast cancer cell lines, investigate their molecular interactions with five key cancer-related proteins (Bcl-2, Caspase-3, CDK4, NF-κB, and MMP-9), and assess their pharmacokinetic and toxicity profiles. Cytotoxicity was tested using the MTT assay across five breast cancer cell lines: MCF-7, T47D, MDA-MB-231, BT-474, and 4T1. Vincristine exhibited the most potent cytotoxicity (IC₅₀: 0.05–0.10 µM), followed by vinblastine and camptothecin. Triple-negative breast cancer (TNBC) cells demonstrated higher resistance compared to luminal subtypes, indicating subtype-specific drug responses. Structure–activity relationship analysis revealed that the presence of lactone rings and hydrophobic side chains enhanced cytotoxic activity. Molecular docking using AutoDock 4.2 identified irinotecan, sanguinarine, and piperine as top binders, with binding affinities ranging from –8.5 to –10.9 kcal/mol. Molecular dynamics simulations confirmed the stability of ligand–target interactions (RMSF < 3 Å). ADMET predictions using SwissADME and pkCSM indicated that all three compounds possessed favorable drug-like properties and high gastrointestinal absorption, though sanguinarine and piperine showed potential mutagenicity or carcinogenicity. The integrated in vitro and in silico approach supports the further exploration of irinotecan, sanguinarine, and piperine as promising multi-target anticancer agents. Notably, tylophorine and vincristine also emerged as potent candidates with favorable pharmacological profiles, warranting further preclinical validation for breast cancer therapy.
References
Agu PC, Afiukwa CA, Orji OU, Ezeh EM, Ofoke IH, Ogbu CO, Ugwuja EI, Aja PM. Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci Rep. 2023 Aug 17;13(1):13398. doi: 10.1038/s41598-023-40160-2.
Alsedfy MY, Ebnalwaled AA, Moustafa M, Said AH. Investigating the binding affinity, molecular dynamics, and ADMET properties of curcumin-IONPs as a mucoadhesive bioavailable oral treatment for iron deficiency anemia. Sci Rep. 2024 Sep 25;14(1):22027. doi: 10.1038/s41598-024-72577-8.
Azmal M, Paul JK, Prima FS, Talukder OF, Ghosh A. An in silico molecular docking and simulation study to identify potential anticancer phytochemicals targeting the RAS signaling pathway. PLoS One. 2024 Sep 19;19(9):e0310637. doi: 10.1371/journal.pone.0310637.
Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024 Jul 5;52(W1):W513-W520. doi: 10.1093/nar/gkae303.
Berlin CB, Sharma E, Kozlowski MC. Quantification of Hydrogen-Bond-Donating Ability of Biologically Relevant Compounds. J Org Chem. 2024 Apr 5;89(7):4684-4690. doi: 10.1021/acs.joc.3c02939.
Badaczewska-Dawid A, Wróblewski K, Kurcinski M, Kmiecik S. Structure prediction of linear and cyclic peptides using CABS-flex. Brief Bioinform. 2024 Jan 22;25(2):bbae003. doi: 10.1093/bib/bbae003.
Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016). Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nature Reviews Clinical Oncology, 13(11), 674–690. https://doi.org/10.1038/nrclinonc.2016.66
Chen D, Oezguen N, Urvil P, Ferguson C, Dann SM, Savidge TC. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Sci Adv. 2016 Mar 25;2(3):e1501240. doi: 10.1126/sciadv.1501240.
Chen, Y., Lee, J., & Kim, H. (2023). Comparison of statistical methods for cytotoxicity data analysis in natural product drug discovery. Scientific Reports, 13, 9421. https://doi.org/10.1038/s41598-023-39257-8
Cheng, L. et al. (2021). Biological activities and anticancer potential of indole alkaloids. Phytomedicine.
Durán-Iturbide NA, Díaz-Eufracio BI, Medina-Franco JL. In Silico ADME/Tox Profiling of Natural Products: A Focus on BIOFACQUIM. ACS Omega. 2020 Jun 25;5(26):16076-16084. doi: 10.1021/acsomega.0c01581.
Gu Y, Yu Z, Wang Y, Chen L, Lou C, Yang C, Li W, Liu G, Tang Y. admetSAR3.0: a comprehensive platform for exploration, prediction and optimization of chemical ADMET properties. Nucleic Acids Res. 2024 Jul 5;52(W1):W432-W438. doi: 10.1093/nar/gkae298.
Huang, Y. et al. (2022). Tylophorine inhibits tumor growth through transcriptional repression and inflammation modulation. Molecular Oncology.
Jordan, M. A., & Wilson, L. (2004). Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 4(4), 253–265. https://doi.org/10.1038/nrc1317
Kharisma VD, Ansori ANM, Widyananda MH, Utami SL. Molecular simulation: The potency of conserved region on E6 HPV-16 as a binding target of black tea compounds against cervical cancer. 2020; 20(1): 2795 - 2802. DOI: 10.35124/bca.2020.20.S1.2795
Kumar GS, Moustafa M, Sahoo AK, Malý P, Bharadwaj S. Computational Investigations on the Natural Small Molecule as an Inhibitor of Programmed Death Ligand 1 for Cancer Immunotherapy. Life (Basel). 2022 Apr 29;12(5):659. doi: 10.3390/life12050659.
Li, Y., Zhao, S., & Wang, L. (2022). Structural diversity and anticancer potential of indole alkaloids. Medicinal Research Reviews, 42(5), 1723–1760. https://doi.org/10.1002/med.21861 Perez, E. A. (2009). Microtubule inhibitors: differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Molecular Cancer Therapeutics, 8(8), 2086–2095. https://doi.org/10.1158/1535-7163.MCT-09-0366
Li, J. et al. (2021). Molecular targets in breast cancer: current advances and therapeutic potential. Frontiers in Oncology.
Liu Y, Yang X, Gan J, Chen S, Xiao ZX, Cao Y. CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Res. 2022 Jul 5;50(W1):W159-W164. doi: 10.1093/nar/gkac394.
Lowe, D. and Ugle, R. (2021). Multi-targeted natural products in breast cancer therapy. Drug Discovery Today.
Millan-Casarrubias EJ, García-Tejeda YV, González-De la Rosa CH, Ruiz-Mazón L, Hernández-Rodríguez YM, Cigarroa-Mayorga OE. Molecular Docking and Pharmacological In Silico Evaluation of Camptothecin and Related Ligands as Promising HER2-Targeted Therapies for Breast Cancer. Curr Issues Mol Biol. 2025 Mar 15;47(3):193. doi: 10.3390/cimb47030193.
Mun CS, Hui LY, Sing LC, Karunakaran R, Ravichandran V. Multi-targeted molecular docking, pharmacokinetics, and drug-likeness evaluation of coumarin based compounds targeting proteins involved in development of COVID-19. Saudi J Biol Sci. 2022 Dec;29(12):103458. doi: 10.1016/j.sjbs.2022.103458.
Niki, T. (2020). Computational drug design and ADMET prediction in oncology. Expert Opinion on Drug Metabolism & Toxicology.
Olofinsan K, Abrahamse H, George BP. Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management. Molecules. 2023 Jul 22;28(14):5578. doi: 10.3390/molecules28145578.
Pfeiffer P, Liposits G, Taarpgaard LS. Angiogenesis inhibitors for metastatic colorectal cancer. Transl Cancer Res. 2023 Dec 31;12(12):3241-3244. doi: 10.21037/tcr-23-1568.
Pommier, Y. (2006). Topoisomerase I inhibitors: camptothecins and beyond. Nature Reviews Cancer, 6(10), 789–802. https://doi.org/10.1038/nrc1977
Rahman MM, Islam MR, Akash S, Mim SA, Rahaman MS, Emran TB, Akkol EK, Sharma R, Alhumaydhi FA, Sweilam SH, Hossain ME, Ray TK, Sultana S, Ahmed M, Sobarzo-Sánchez E, Wilairatana P. In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective. Front Cell Infect Microbiol. 2022 Aug 22;12:929430. doi: 10.3389/fcimb.2022.929430.
Rai M, Singh AV, Paudel N, Kanase A, Falletta E, Kerkar P, Heyda J, Barghash RF, Pratap Singh S, Soos M. Herbal concoction Unveiled: A computational analysis of phytochemicals' pharmacokinetic and toxicological profiles using novel approach methodologies (NAMs). Curr Res Toxicol. 2023 Aug 12;5:100118. doi: 10.1016/j.crtox.2023.100118.
Roché, H., Vahdat, L. T., & Delord, J. P. (2010). Vinorelbine: a valuable cytotoxic in the management of breast cancer. Clinical Breast Cancer, 10(1), 18–25. https://doi.org/10.3816/CBC.2010.n.003
Rodríguez-García, A., Hernández, M., & Torres, L. (2023). Computational evaluation of pharmacokinetics and toxicity of phytochemicals using SwissADME and pkCSM. Frontiers in Pharmacology, 14, 1172350. https://doi.org/10.3389/fphar.2023.1172350
Russell G. Theoretical evaluation of the biological activity of hydrogen. Med Gas Res. 2025 Jun 1;15(2):266-275. doi: 10.4103/mgr.MEDGASRES-D-24-00083.
Shah, S. et al. (2022). Multi-target strategies in cancer therapy: Advances in natural product research. Pharmacological Research.
Sobarzo-Sánchez E, Wilairatana P. In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective. Front Cell Infect Microbiol. 2022 Aug 22;12:929430. doi: 10.3389/fcimb.2022.929430.
Sung, H. et al. (2021). Global Cancer Statistics 2020. CA: A Cancer Journal for Clinicians.
Tanaka, H., Nakamura, T., & Ito, Y. (2023). Advances in MTT assay standardization for high-throughput anticancer compound screening. Journal of Biomedical Methods, 12(1), 45–53. https://doi.org/10.1016/j.jbm.2023.104522
Tang M, Hu X, Wang Y, Yao X, Zhang W, Yu C, Cheng F, Li J, Fang Q. Ivermectin, a potential anticancer drug derived from an antiparasitic drug. Pharmacol Res. 2021 Jan;163:105207. doi: 10.1016/j.phrs.2020.105207.
Wahyuni DK, Kharisma VD, Murtadlo AAA, Rahmawati CT, Syukriya AJ, Prasongsuk S, Subramaniam S, Wibowo AT, Purnobasuki H. The antioxidant and antimicrobial activity of ethanolic extract in roots, stems, and leaves of three commercial Cymbopogon species. BMC Complement Med Ther. 2024 Jul 18;24(1):272. doi: 10.1186/s12906-024-04573-4.
Wahyuni DK, Wacharasindhu S, Bankeeree W, Punnapayak H, Purnobasuki H, Junairiah J, Ansori ANM, Kharisma VD, Parikesit AA, Suhargo L, Prasongsuk S. Molecular simulation of compounds from n-hexane fraction of Sonchus arvensis L. leaves as SARS-CoV-2 antiviral through inhibitor activity targeting strategic viral protein. 2022; 10(6): 1126 - 1138. DOI: 10.56499/jppres22.1489_10.6.1126
Wang D, Jin J, Shi G, Bao J, Wang Z, Li S, Pan P, Li D, Kang Y, Hou T. ADMET evaluation in drug discovery: 21. Application and industrial validation of machine learning algorithms for Caco-2 permeability prediction. J Cheminform. 2025 Jan 10;17(1):3. doi: 10.1186/s13321-025-00947-z.
Wang, M. and Li, C. (2021). Integrating docking and toxicity prediction in early cancer drug discovery. Journal of Chemical Information and Modeling.
Wijaya RM, Hafidzhah MA, Kharisma VD, Ansori ANM, Parikesit AA. COVID-19 In Silico Drug with Zingiber officinale Natural Product Compound Library Targeting the Mpro Protein. 2021; 25(3): 162-171. doi: 10.7454/mss.v25i3.1244.
Wu C, Wong AR, Chen Q, Yang S, Chen M, Sun X, Zhou L, Liu Y, Yang AWH, Bi J, Hung A, Li H, Zhao X. Identification of inhibitors from a functional food-based plant Perillae Folium against hyperuricemia via metabolomics profiling, network pharmacology and all-atom molecular dynamics simulations. Front Endocrinol (Lausanne). 2024 Feb 16;15:1320092. doi: 10.3389/fendo.2024.1320092.
Yamada, S., Watanabe, K., & Fujioka, M. (2024). Molecular docking-guided discovery of natural multitarget inhibitors in breast cancer. Computational Biology and Chemistry, 104, 107939. https://doi.org/10.1016/j.compbiolchem.2024.107939
Yang Z, Xia L. Resveratrol inhibits the proliferation, invasion, and migration, and induces the apoptosis of human gastric cancer cells through the MALAT1/miR-383-5p/DDIT4 signaling pathway. J Gastrointest Oncol. 2022 Jun;13(3):985-996. doi: 10.21037/jgo-22-307.
Yun D, Yoon SY, Park SJ, Park YJ. The Anticancer Effect of Natural Plant Alkaloid Isoquinolines. Int J Mol Sci. 2021 Feb 6;22(4):1653. doi: 10.3390/ijms22041653.
Zhao G, Liu X, Wang S, Bai Z, Zhang S, Wang Y, Yu H, Xu X. Hydrogen bonding penalty used for virtual screening to discover potent inhibitors for Papain-Like cysteine proteases of SARS-CoV-2. Chem Biol Drug Des. 2022 Oct;100(4):502-514. doi: 10.1111/cbdd.14115.
Zhao, Z. and Ren, X. (2022). Therapy resistance in breast cancer: mechanisms and solutions. Cancer Cell International.
Alsedfy MY, Ebnalwaled AA, Moustafa M, Said AH. Investigating the binding affinity, molecular dynamics, and ADMET properties of curcumin-IONPs as a mucoadhesive bioavailable oral treatment for iron deficiency anemia. Sci Rep. 2024 Sep 25;14(1):22027. doi: 10.1038/s41598-024-72577-8.
Azmal M, Paul JK, Prima FS, Talukder OF, Ghosh A. An in silico molecular docking and simulation study to identify potential anticancer phytochemicals targeting the RAS signaling pathway. PLoS One. 2024 Sep 19;19(9):e0310637. doi: 10.1371/journal.pone.0310637.
Banerjee P, Kemmler E, Dunkel M, Preissner R. ProTox 3.0: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res. 2024 Jul 5;52(W1):W513-W520. doi: 10.1093/nar/gkae303.
Berlin CB, Sharma E, Kozlowski MC. Quantification of Hydrogen-Bond-Donating Ability of Biologically Relevant Compounds. J Org Chem. 2024 Apr 5;89(7):4684-4690. doi: 10.1021/acs.joc.3c02939.
Badaczewska-Dawid A, Wróblewski K, Kurcinski M, Kmiecik S. Structure prediction of linear and cyclic peptides using CABS-flex. Brief Bioinform. 2024 Jan 22;25(2):bbae003. doi: 10.1093/bib/bbae003.
Bianchini, G., Balko, J. M., Mayer, I. A., Sanders, M. E., & Gianni, L. (2016). Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nature Reviews Clinical Oncology, 13(11), 674–690. https://doi.org/10.1038/nrclinonc.2016.66
Chen D, Oezguen N, Urvil P, Ferguson C, Dann SM, Savidge TC. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Sci Adv. 2016 Mar 25;2(3):e1501240. doi: 10.1126/sciadv.1501240.
Chen, Y., Lee, J., & Kim, H. (2023). Comparison of statistical methods for cytotoxicity data analysis in natural product drug discovery. Scientific Reports, 13, 9421. https://doi.org/10.1038/s41598-023-39257-8
Cheng, L. et al. (2021). Biological activities and anticancer potential of indole alkaloids. Phytomedicine.
Durán-Iturbide NA, Díaz-Eufracio BI, Medina-Franco JL. In Silico ADME/Tox Profiling of Natural Products: A Focus on BIOFACQUIM. ACS Omega. 2020 Jun 25;5(26):16076-16084. doi: 10.1021/acsomega.0c01581.
Gu Y, Yu Z, Wang Y, Chen L, Lou C, Yang C, Li W, Liu G, Tang Y. admetSAR3.0: a comprehensive platform for exploration, prediction and optimization of chemical ADMET properties. Nucleic Acids Res. 2024 Jul 5;52(W1):W432-W438. doi: 10.1093/nar/gkae298.
Huang, Y. et al. (2022). Tylophorine inhibits tumor growth through transcriptional repression and inflammation modulation. Molecular Oncology.
Jordan, M. A., & Wilson, L. (2004). Microtubules as a target for anticancer drugs. Nature Reviews Cancer, 4(4), 253–265. https://doi.org/10.1038/nrc1317
Kharisma VD, Ansori ANM, Widyananda MH, Utami SL. Molecular simulation: The potency of conserved region on E6 HPV-16 as a binding target of black tea compounds against cervical cancer. 2020; 20(1): 2795 - 2802. DOI: 10.35124/bca.2020.20.S1.2795
Kumar GS, Moustafa M, Sahoo AK, Malý P, Bharadwaj S. Computational Investigations on the Natural Small Molecule as an Inhibitor of Programmed Death Ligand 1 for Cancer Immunotherapy. Life (Basel). 2022 Apr 29;12(5):659. doi: 10.3390/life12050659.
Li, Y., Zhao, S., & Wang, L. (2022). Structural diversity and anticancer potential of indole alkaloids. Medicinal Research Reviews, 42(5), 1723–1760. https://doi.org/10.1002/med.21861 Perez, E. A. (2009). Microtubule inhibitors: differentiating tubulin-inhibiting agents based on mechanisms of action, clinical activity, and resistance. Molecular Cancer Therapeutics, 8(8), 2086–2095. https://doi.org/10.1158/1535-7163.MCT-09-0366
Li, J. et al. (2021). Molecular targets in breast cancer: current advances and therapeutic potential. Frontiers in Oncology.
Liu Y, Yang X, Gan J, Chen S, Xiao ZX, Cao Y. CB-Dock2: improved protein-ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Res. 2022 Jul 5;50(W1):W159-W164. doi: 10.1093/nar/gkac394.
Lowe, D. and Ugle, R. (2021). Multi-targeted natural products in breast cancer therapy. Drug Discovery Today.
Millan-Casarrubias EJ, García-Tejeda YV, González-De la Rosa CH, Ruiz-Mazón L, Hernández-Rodríguez YM, Cigarroa-Mayorga OE. Molecular Docking and Pharmacological In Silico Evaluation of Camptothecin and Related Ligands as Promising HER2-Targeted Therapies for Breast Cancer. Curr Issues Mol Biol. 2025 Mar 15;47(3):193. doi: 10.3390/cimb47030193.
Mun CS, Hui LY, Sing LC, Karunakaran R, Ravichandran V. Multi-targeted molecular docking, pharmacokinetics, and drug-likeness evaluation of coumarin based compounds targeting proteins involved in development of COVID-19. Saudi J Biol Sci. 2022 Dec;29(12):103458. doi: 10.1016/j.sjbs.2022.103458.
Niki, T. (2020). Computational drug design and ADMET prediction in oncology. Expert Opinion on Drug Metabolism & Toxicology.
Olofinsan K, Abrahamse H, George BP. Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management. Molecules. 2023 Jul 22;28(14):5578. doi: 10.3390/molecules28145578.
Pfeiffer P, Liposits G, Taarpgaard LS. Angiogenesis inhibitors for metastatic colorectal cancer. Transl Cancer Res. 2023 Dec 31;12(12):3241-3244. doi: 10.21037/tcr-23-1568.
Pommier, Y. (2006). Topoisomerase I inhibitors: camptothecins and beyond. Nature Reviews Cancer, 6(10), 789–802. https://doi.org/10.1038/nrc1977
Rahman MM, Islam MR, Akash S, Mim SA, Rahaman MS, Emran TB, Akkol EK, Sharma R, Alhumaydhi FA, Sweilam SH, Hossain ME, Ray TK, Sultana S, Ahmed M, Sobarzo-Sánchez E, Wilairatana P. In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective. Front Cell Infect Microbiol. 2022 Aug 22;12:929430. doi: 10.3389/fcimb.2022.929430.
Rai M, Singh AV, Paudel N, Kanase A, Falletta E, Kerkar P, Heyda J, Barghash RF, Pratap Singh S, Soos M. Herbal concoction Unveiled: A computational analysis of phytochemicals' pharmacokinetic and toxicological profiles using novel approach methodologies (NAMs). Curr Res Toxicol. 2023 Aug 12;5:100118. doi: 10.1016/j.crtox.2023.100118.
Roché, H., Vahdat, L. T., & Delord, J. P. (2010). Vinorelbine: a valuable cytotoxic in the management of breast cancer. Clinical Breast Cancer, 10(1), 18–25. https://doi.org/10.3816/CBC.2010.n.003
Rodríguez-García, A., Hernández, M., & Torres, L. (2023). Computational evaluation of pharmacokinetics and toxicity of phytochemicals using SwissADME and pkCSM. Frontiers in Pharmacology, 14, 1172350. https://doi.org/10.3389/fphar.2023.1172350
Russell G. Theoretical evaluation of the biological activity of hydrogen. Med Gas Res. 2025 Jun 1;15(2):266-275. doi: 10.4103/mgr.MEDGASRES-D-24-00083.
Shah, S. et al. (2022). Multi-target strategies in cancer therapy: Advances in natural product research. Pharmacological Research.
Sobarzo-Sánchez E, Wilairatana P. In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective. Front Cell Infect Microbiol. 2022 Aug 22;12:929430. doi: 10.3389/fcimb.2022.929430.
Sung, H. et al. (2021). Global Cancer Statistics 2020. CA: A Cancer Journal for Clinicians.
Tanaka, H., Nakamura, T., & Ito, Y. (2023). Advances in MTT assay standardization for high-throughput anticancer compound screening. Journal of Biomedical Methods, 12(1), 45–53. https://doi.org/10.1016/j.jbm.2023.104522
Tang M, Hu X, Wang Y, Yao X, Zhang W, Yu C, Cheng F, Li J, Fang Q. Ivermectin, a potential anticancer drug derived from an antiparasitic drug. Pharmacol Res. 2021 Jan;163:105207. doi: 10.1016/j.phrs.2020.105207.
Wahyuni DK, Kharisma VD, Murtadlo AAA, Rahmawati CT, Syukriya AJ, Prasongsuk S, Subramaniam S, Wibowo AT, Purnobasuki H. The antioxidant and antimicrobial activity of ethanolic extract in roots, stems, and leaves of three commercial Cymbopogon species. BMC Complement Med Ther. 2024 Jul 18;24(1):272. doi: 10.1186/s12906-024-04573-4.
Wahyuni DK, Wacharasindhu S, Bankeeree W, Punnapayak H, Purnobasuki H, Junairiah J, Ansori ANM, Kharisma VD, Parikesit AA, Suhargo L, Prasongsuk S. Molecular simulation of compounds from n-hexane fraction of Sonchus arvensis L. leaves as SARS-CoV-2 antiviral through inhibitor activity targeting strategic viral protein. 2022; 10(6): 1126 - 1138. DOI: 10.56499/jppres22.1489_10.6.1126
Wang D, Jin J, Shi G, Bao J, Wang Z, Li S, Pan P, Li D, Kang Y, Hou T. ADMET evaluation in drug discovery: 21. Application and industrial validation of machine learning algorithms for Caco-2 permeability prediction. J Cheminform. 2025 Jan 10;17(1):3. doi: 10.1186/s13321-025-00947-z.
Wang, M. and Li, C. (2021). Integrating docking and toxicity prediction in early cancer drug discovery. Journal of Chemical Information and Modeling.
Wijaya RM, Hafidzhah MA, Kharisma VD, Ansori ANM, Parikesit AA. COVID-19 In Silico Drug with Zingiber officinale Natural Product Compound Library Targeting the Mpro Protein. 2021; 25(3): 162-171. doi: 10.7454/mss.v25i3.1244.
Wu C, Wong AR, Chen Q, Yang S, Chen M, Sun X, Zhou L, Liu Y, Yang AWH, Bi J, Hung A, Li H, Zhao X. Identification of inhibitors from a functional food-based plant Perillae Folium against hyperuricemia via metabolomics profiling, network pharmacology and all-atom molecular dynamics simulations. Front Endocrinol (Lausanne). 2024 Feb 16;15:1320092. doi: 10.3389/fendo.2024.1320092.
Yamada, S., Watanabe, K., & Fujioka, M. (2024). Molecular docking-guided discovery of natural multitarget inhibitors in breast cancer. Computational Biology and Chemistry, 104, 107939. https://doi.org/10.1016/j.compbiolchem.2024.107939
Yang Z, Xia L. Resveratrol inhibits the proliferation, invasion, and migration, and induces the apoptosis of human gastric cancer cells through the MALAT1/miR-383-5p/DDIT4 signaling pathway. J Gastrointest Oncol. 2022 Jun;13(3):985-996. doi: 10.21037/jgo-22-307.
Yun D, Yoon SY, Park SJ, Park YJ. The Anticancer Effect of Natural Plant Alkaloid Isoquinolines. Int J Mol Sci. 2021 Feb 6;22(4):1653. doi: 10.3390/ijms22041653.
Zhao G, Liu X, Wang S, Bai Z, Zhang S, Wang Y, Yu H, Xu X. Hydrogen bonding penalty used for virtual screening to discover potent inhibitors for Papain-Like cysteine proteases of SARS-CoV-2. Chem Biol Drug Des. 2022 Oct;100(4):502-514. doi: 10.1111/cbdd.14115.
Zhao, Z. and Ren, X. (2022). Therapy resistance in breast cancer: mechanisms and solutions. Cancer Cell International.
Published
2025-08-22
How to Cite
Rollando, R., Viol Dhea Kharisma, & Arif N. M. Ansori. (2025). Cytotoxic and Computational Profiling of 20 Indole Alkaloids Across Five Breast Cancer Cell Lines. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.21436
Issue
Section
Research Article
