Molecular Docking and ADME Analysis of the novel compound [(Z)-1a,5-dimethyl-9-methylene-8-oxo1a,2,3,6,6a,8,9,9a,10,10a-decahydro-11-oxa bicyclo(8.1.0) undeca-1(10),4-dieno(7,8-b) furan-10-yl acetate] isolated from Tanacetum dolicophyllum (Kitam.) Kitam
Article Main
Abstract
In contemporary drug design, molecular docking is essential for understanding drug-receptor interactions. The present study aimed to use molecular docking to determine the anticancer potential of the bioactive compound [(Z)-1a,5-dimethyl-9-methylene-8-oxo 1a,2,3,6,6a,8,9,9a,10,10a-decahydro-11-oxa-bicyclo (8.1.0) undeca-1(10),4-dieno(7,8-b) furan-10-yl acetate] isolated from Tanacetum dolicophyllum (Kitam.) Kitam. The outcome demonstrated that the molecule obtained from T. dolicophyllum binds with a stronger affinity and lower free energy than roflumilast (the control ligand), with 1XMU exhibiting a glide score of -6.379 Kcal/mol and -6.14 Kcal/mol, respectively. When the binding energy is negative, the ligand and target protein are well aligned, which may have therapeutic benefits in suppressing microbial activity. Additionally, as determined by in-silico Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) calculations, the synthesized compound validates the drug-likeness within the specified ranges: molecular weight between 150 and 500g/mol, Topological Surface Area (TPSA) polarity between 20 and 130 Å2, lipophilicity between -0.7 and +5.0, Log S not exceeding 6, flexibility not exceeding 9, and saturation not less than 0.25. An evaluation of docking score and ADME properties reveals that the synthesized compound exhibits notable characteristics, positioning it as a promising candidate for drug development. The compound showed adherence to these requirements, indicating favorable in-vivo drug penetration and absorption properties.
Article Details
Article Details
Keywords
Anticancer, Drug penetration, Lipinski’s rule of five, Molecular docking, Roflumilast
References
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Daina, A., Michielin, O. & Zoete, V. (2014). iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. Journal of Chemical Information and Modeling., 54(12), 3284-301. https://doi.org/10.1021/ci500467k
Daina, A., Michielin, O. & Zoete, V.J. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep., 7, 42717. https://doi.org/10.1038/srep42717.
Daina, A. & Zoete, V. (2016). A boiled‐egg to predict gastrointestinal absorption and brain penetration of small molecules. Chem Med Chem., 11(11), 1117-21. https://doi.org/10.1002/cmdc.201600182.
Di, L., Artursson, P., Avdeef, A., Ecker, G.F., Faller, B., Fischer, H., Houston, J.B., Kansy, M., Kerns, E.H., Krämer, S.D. & Lennernäs, H. (2012). Evidence-based approach to assess passive diffusion and carrier-mediated drug transport. Drug Discovery Today., 17(15-16), 905-12.
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Friesner, R.A., Murphy, R.B., Repasky, M.P., Frye, L.L., Greenwood, J.R., Halgren, T.A., Sanschagrin, P.C. & Mainz, D.T. (2006). Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein− ligand complexes. Journal of Medicinal Chemistry., 49(21), 6177-96. https://doi.org/10.1021/jm051256o
Gnana, M., Ruba, P., Prasanth, M.L., Lalchand, D., Shaik, K. & Kumar S. (2024). Synthesis, DNA binding, molecular docking and anticancer studies of copper (ii), nickel (ii), and zinc (ii) complexes of primaquine-based ligand. International Journal of Pharmaceutical Quality Assurance., 15(1), 69-75.
Hann, M.M. & Keserü, G.M. (2012). Finding the sweet spot: the role of nature and nurture in medicinal chemistry. Nature Reviews Drug Discovery., 11(5), 355-65. https://doi.org/10.1038/nrd3701
Lee, K. & Kim, D. (2019). In-silico molecular binding prediction for human drug targets using deep neural multi-task learning. Genes., 10(11), 906. https://doi.org/10.3390/genes10110906
Leeson, P.D. & Springthorpe, B. (2007). The influence of drug-like concepts on decision-making in medicinal chemistry. Nature Reviews Drug discovery., 6(11), 881-90. https://doi.org/10.1038/nrd24451
Lipinski, C.A., Lombardo, F., Dominy, B.W. & Feeney, P.J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews., 64, 4-17. https://doi.org/10.1016/j.addr.2012.09.019
Liu, X., Testa, B. & Fahr, A. (2011). Lipophilicity and its relationship with passive drug permeation. Pharmaceutical Research., 962-77.
https://doi.org/10.1007/s11095-010-0303-7
Luca, M., Raquel, P., Ismael, G., Ricard, G.S., Scott, B. & Jordi, M. (2025). Refined ADME Profiles for ATC Drug Classes. Pharmaceutics., 17(3), 308. https://doi.org/10.3390/pharmaceutics17030308
Matlock, M.K., Hughes, T.B., Dahlin, J.L. & Swamidass, S.J. (2018). Modeling small-molecule reactivity identifies promiscuous bioactive compounds. Journal of Chemical Information and Modeling., 58(8), 1483-500.
https://doi.org/10.1021/acs.jcim.8b00104
Montanari, F. & Ecker, G.F. (2015). Prediction of drug–ABC-transporter interaction—Recent advances and future challenges. Advanced drug delivery reviews., 86, 17-26. https://doi.org/10.1016/j.addr.2015.03.001
Mujawar, T., Tare, H., Deshmukh, N., Udugade, B. & Thube, U. (2023). Repurposing FDA-Approved Anastrozole-based Drugs for Breast Cancer through Drug-Drug Transcriptomic Similarity and Cavity Detection Guided Blind Docking. International Journal of Drug Delivery Technology., 13(4), 1173-1177.
Ndombera, F., Maiyoh, G. & Tuei, V. (2019). Pharmacokinetic, physicochemical and medicinal properties of n-glycoside anti-cancer agent more potent than 2-deoxy-d-glucose in lung cancer cells. Journal of Pharmacy and Pharmacology., 7(4), 165-176. DOI:10.17265/2328-2150/2019.04.003
O'Boyle, N.M., Banck, M., James, C.A., Morley, C., Vandermeersch, T. & Hutchison, G.R. (2011). Open Babel: An open chemical toolbox. Journal of cheminformatics., 3, 1-4. https://doi.org/10.1186/1758-2946-3-33
Ogu, C.C. & Maxa, J.L. (2000). Drug interactions due to cytochrome P450. Taylor & Francis., 13(4), 421-423.
https://doi.org/10.1080/08998280.2000.11927719
Sable, V. & Ahire, G. (2024). Network Pharmacology and Molecular Docking Technology-based Strategy to Explore the Potential Mechanism of Diabecon Formulation Botanicals. International Journal of Drug Delivery Technology., 14(1), 274-280.
Savjani, K.T., Gajjar, A.K. & Savjani, J.K. (2012). Drug solubility: importance and enhancement techniques. ISRN pharmaceutics., doi:10.5402/2012/195727
Schrodinger Release 2018 version 2 LigPrep. New York: Schrodinger, LLC, 2018.
Sean, E., Thomas, R.L., Fabio, U. & Ana, C.P. (2024). In silico ADME/tox comes of age: twenty years later. Xenobiotica., 54(7), 352-358. https://doi.org/10.1080/00498254.2023.2245049
Sharma, N.K., Jha, K.K. & Priyanka. (2010). Molecular docking: an overview. J. Adv. Sci. Res.,1(1), 67-72.
Sliwoski, G., Kothiwale, S., Meiler, J. & Lowe, E.W. (2014). Computational methods in drug discovery. Pharmacological reviews., 66(1), 334-95. doi: 10.1124/pr.112.007336
Tajane, P., Deshmukh, S., Lunkad, A., Tare, M. & Bhise, M. (2024). Discovery of Mitogen-Activated Protein Kinase for Melanoma Using Melphalan Based Hybrid Classic 3-Point Pharmacophore Virtual Screening and Molecular Docking Approach. International Journal of Pharmaceutical Quality Assurance., 15(2), 712-719.
Teague, S.J., Davis, A.M., Leeson, P.D. & Oprea, T. (1999). The design of lead-like combinatorial libraries. Angewandte Chemie International Edition., 38(24), 3743-8.
Testa, B., Crivori, P., Reist, M. & Carrupt, P.A. (2000). The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples. Perspectives in Drug Discovery and Design., 179-211. https://doi.org/10.1023/A:1008741731244
Vijesh, A.A., Isloor, A.M., Telkar, S., Peethambar, S.K., Rai, S. & Isloor, N. (2011). Synthesis, characterization and antimicrobial studies of some new pyrazole incorporated imidazole derivatives. European Journal of Medicinal Chemistry., 46(8), 3531-6. https://doi.org/10.1016/j.ejmech.2011.05.005
Yalkowsky, S.H. & Valvani, S.C. (1980). Solubility and partitioning I: solubility of nonelectrolytes in water. Journal of Pharmaceutical Sciences. 69(8), 912-22. https://doi.org/10.1002/jps.2600690814
Alland, C., Moreews, F., Boens, D., Carpentier, M., Chiusa, S., Lonquety, M., Renault, N., Wong, Y., Cantalloube, H., Chomilier, J. & Hochez, J. (2005). RPBS: a web resource for structural bioinformatics. Nucleic AcidsRresearch., 1, 33-49. https://doi.org/10.1093/nar/gki477.
Amidon, G.L., Lennernäs, H., Shah, V.P. & Crison JR. (1995). A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research. 12, 413-20. https://doi.org/10.1023/A:1016212804288.
Arnott, J.A. & Planey, S.L. (2012). The influence of lipophilicity in drug discovery and design. Expert Opinion on Drug Discovery., 1, 863-75. https://doi.org/10.1517/17460441.2012.714363
Baell, J.B. & Holloway, G.A. (2010). New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. Journal of Medicinal Chemistry., 8(53), 2719-40. https://doi.org/10.1021/jm901137j.
Bharathi, A., Roopan, S.M., Vasavi, C.S., Munusami, P., Gayathri, G.A. & Gayathri, M. (2014). In Silico Molecular Docking and In Vitro Antidiabetic Studies of Dihydropyrimido [4, 5‐a] acridin‐2‐amines. BioMed Research International., 2014(1), 971569. https://doi.org/10.1155/2014/971569
Brenk, R., Schipani, A., James, D., Krasowski, A., Gilbert, I.H., Frearson, J. & Wyatt, P.G. (2008). Lessons learnt from assembling screening libraries for drug discovery for neglected diseases. ChemMedChem: Chemistry Enabling Drug Discovery., 3(3), 435-44. https://doi.org/10.1002/cmdc.200700139
Brito‐Sánchez, Y., Marrero‐Ponce, Y., Barigye, S.J., Yaber‐Goenaga, I., Morell Perez, C., Le‐Thi‐Thu, H. & Cherkasov, A. (2015). Towards better BBB passage prediction using an extensive and curated data set. Molecular Informatics., 34(5), 308-30. https://doi.org/10.1002/minf.201400118
Cho, J.Y. & Park, J. (2008). Contribution of natural inhibitors to the understanding of the PI3K/PDK1/PKB pathway in the insulin-mediated intracellular signaling cascade. International Journal of Molecular Sciences., 9(11), 2217-30. https://doi.org/10.3390/ijms9112217.
Daina, A., Michielin, O. & Zoete, V. (2014). iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. Journal of Chemical Information and Modeling., 54(12), 3284-301. https://doi.org/10.1021/ci500467k
Daina, A., Michielin, O. & Zoete, V.J. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep., 7, 42717. https://doi.org/10.1038/srep42717.
Daina, A. & Zoete, V. (2016). A boiled‐egg to predict gastrointestinal absorption and brain penetration of small molecules. Chem Med Chem., 11(11), 1117-21. https://doi.org/10.1002/cmdc.201600182.
Di, L., Artursson, P., Avdeef, A., Ecker, G.F., Faller, B., Fischer, H., Houston, J.B., Kansy, M., Kerns, E.H., Krämer, S.D. & Lennernäs, H. (2012). Evidence-based approach to assess passive diffusion and carrier-mediated drug transport. Drug Discovery Today., 17(15-16), 905-12.
Egan, W.J., Merz, K.M. & Baldwin, J.J. (2000). Prediction of drug absorption using multivariate statistics. Journal of Medicinal Chemistry., 43(21), 3867-77. https://doi.org/10.1021/jm000292e.
Friesner, R.A., Murphy, R.B., Repasky, M.P., Frye, L.L., Greenwood, J.R., Halgren, T.A., Sanschagrin, P.C. & Mainz, D.T. (2006). Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein− ligand complexes. Journal of Medicinal Chemistry., 49(21), 6177-96. https://doi.org/10.1021/jm051256o
Gnana, M., Ruba, P., Prasanth, M.L., Lalchand, D., Shaik, K. & Kumar S. (2024). Synthesis, DNA binding, molecular docking and anticancer studies of copper (ii), nickel (ii), and zinc (ii) complexes of primaquine-based ligand. International Journal of Pharmaceutical Quality Assurance., 15(1), 69-75.
Hann, M.M. & Keserü, G.M. (2012). Finding the sweet spot: the role of nature and nurture in medicinal chemistry. Nature Reviews Drug Discovery., 11(5), 355-65. https://doi.org/10.1038/nrd3701
Lee, K. & Kim, D. (2019). In-silico molecular binding prediction for human drug targets using deep neural multi-task learning. Genes., 10(11), 906. https://doi.org/10.3390/genes10110906
Leeson, P.D. & Springthorpe, B. (2007). The influence of drug-like concepts on decision-making in medicinal chemistry. Nature Reviews Drug discovery., 6(11), 881-90. https://doi.org/10.1038/nrd24451
Lipinski, C.A., Lombardo, F., Dominy, B.W. & Feeney, P.J. (2012). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews., 64, 4-17. https://doi.org/10.1016/j.addr.2012.09.019
Liu, X., Testa, B. & Fahr, A. (2011). Lipophilicity and its relationship with passive drug permeation. Pharmaceutical Research., 962-77.
https://doi.org/10.1007/s11095-010-0303-7
Luca, M., Raquel, P., Ismael, G., Ricard, G.S., Scott, B. & Jordi, M. (2025). Refined ADME Profiles for ATC Drug Classes. Pharmaceutics., 17(3), 308. https://doi.org/10.3390/pharmaceutics17030308
Matlock, M.K., Hughes, T.B., Dahlin, J.L. & Swamidass, S.J. (2018). Modeling small-molecule reactivity identifies promiscuous bioactive compounds. Journal of Chemical Information and Modeling., 58(8), 1483-500.
https://doi.org/10.1021/acs.jcim.8b00104
Montanari, F. & Ecker, G.F. (2015). Prediction of drug–ABC-transporter interaction—Recent advances and future challenges. Advanced drug delivery reviews., 86, 17-26. https://doi.org/10.1016/j.addr.2015.03.001
Mujawar, T., Tare, H., Deshmukh, N., Udugade, B. & Thube, U. (2023). Repurposing FDA-Approved Anastrozole-based Drugs for Breast Cancer through Drug-Drug Transcriptomic Similarity and Cavity Detection Guided Blind Docking. International Journal of Drug Delivery Technology., 13(4), 1173-1177.
Ndombera, F., Maiyoh, G. & Tuei, V. (2019). Pharmacokinetic, physicochemical and medicinal properties of n-glycoside anti-cancer agent more potent than 2-deoxy-d-glucose in lung cancer cells. Journal of Pharmacy and Pharmacology., 7(4), 165-176. DOI:10.17265/2328-2150/2019.04.003
O'Boyle, N.M., Banck, M., James, C.A., Morley, C., Vandermeersch, T. & Hutchison, G.R. (2011). Open Babel: An open chemical toolbox. Journal of cheminformatics., 3, 1-4. https://doi.org/10.1186/1758-2946-3-33
Ogu, C.C. & Maxa, J.L. (2000). Drug interactions due to cytochrome P450. Taylor & Francis., 13(4), 421-423.
https://doi.org/10.1080/08998280.2000.11927719
Sable, V. & Ahire, G. (2024). Network Pharmacology and Molecular Docking Technology-based Strategy to Explore the Potential Mechanism of Diabecon Formulation Botanicals. International Journal of Drug Delivery Technology., 14(1), 274-280.
Savjani, K.T., Gajjar, A.K. & Savjani, J.K. (2012). Drug solubility: importance and enhancement techniques. ISRN pharmaceutics., doi:10.5402/2012/195727
Schrodinger Release 2018 version 2 LigPrep. New York: Schrodinger, LLC, 2018.
Sean, E., Thomas, R.L., Fabio, U. & Ana, C.P. (2024). In silico ADME/tox comes of age: twenty years later. Xenobiotica., 54(7), 352-358. https://doi.org/10.1080/00498254.2023.2245049
Sharma, N.K., Jha, K.K. & Priyanka. (2010). Molecular docking: an overview. J. Adv. Sci. Res.,1(1), 67-72.
Sliwoski, G., Kothiwale, S., Meiler, J. & Lowe, E.W. (2014). Computational methods in drug discovery. Pharmacological reviews., 66(1), 334-95. doi: 10.1124/pr.112.007336
Tajane, P., Deshmukh, S., Lunkad, A., Tare, M. & Bhise, M. (2024). Discovery of Mitogen-Activated Protein Kinase for Melanoma Using Melphalan Based Hybrid Classic 3-Point Pharmacophore Virtual Screening and Molecular Docking Approach. International Journal of Pharmaceutical Quality Assurance., 15(2), 712-719.
Teague, S.J., Davis, A.M., Leeson, P.D. & Oprea, T. (1999). The design of lead-like combinatorial libraries. Angewandte Chemie International Edition., 38(24), 3743-8.
Testa, B., Crivori, P., Reist, M. & Carrupt, P.A. (2000). The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples. Perspectives in Drug Discovery and Design., 179-211. https://doi.org/10.1023/A:1008741731244
Vijesh, A.A., Isloor, A.M., Telkar, S., Peethambar, S.K., Rai, S. & Isloor, N. (2011). Synthesis, characterization and antimicrobial studies of some new pyrazole incorporated imidazole derivatives. European Journal of Medicinal Chemistry., 46(8), 3531-6. https://doi.org/10.1016/j.ejmech.2011.05.005
Yalkowsky, S.H. & Valvani, S.C. (1980). Solubility and partitioning I: solubility of nonelectrolytes in water. Journal of Pharmaceutical Sciences. 69(8), 912-22. https://doi.org/10.1002/jps.2600690814
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Molecular Docking and ADME Analysis of the novel compound [(Z)-1a,5-dimethyl-9-methylene-8-oxo1a,2,3,6,6a,8,9,9a,10,10a-decahydro-11-oxa bicyclo(8.1.0) undeca-1(10),4-dieno(7,8-b) furan-10-yl acetate] isolated from Tanacetum dolicophyllum (Kitam.) Kitam. (2025). Journal of Applied and Natural Science, 17(2), 793-801. https://doi.org/10.31018/jans.v17i2.6354
