QSAR of acyl alizarin red biocompound derivatives of Rubia tinctorum roots and its ADMET properties as anti-breast cancer candidates against MMP-9 protein receptor: In Silico study
- Authors: Alifiansyah M.R.1, Herdiansyah M.A.2, Pratiwi R.C.1, Pramesti R.P.1, Hafsyah N.W.1, Rania A.P.1, Putra J.E.2, Cahyono P.A.2, Litazkiyyah .2, Muhammad S.K.3, Murtadlo A.A.2,4, Kharisma V.D.2,4, Ansori A.N.4,5,6, Jakhmola V.7, Ashok P.K.8, Kalra J.M.9, Purnobasuki H.2, Pratiwi I.A.2
-
Affiliations:
- Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga
- Department of Physics, Faculty of Science and Technology, Universitas Airlangga
- Division of Research and Development, Jalan Tengah
- Postgraduate School, Universitas Airlangga
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University
- Gyani Inder Singh Institute of Professional Studies
- School of Pharmaceutical Sciences, Shri Guru Ram Rai University
- Issue: Vol 7, No 2 (2024)
- Pages: 312-320
- Section: Articles
- URL: https://journals.rcsi.science/2618-9771/article/view/311309
- DOI: https://doi.org/10.21323/2618-9771-2024-7-2-312-320
- ID: 311309
Cite item
Full Text
Abstract
Alizarin is a polycyclic compound isolated from roots of Rubia tinctorum that has potential as a breast anticancer candidate. Increasing anticancer activity can be done through structural modification to produce derivatives in the form of group substitution in the meta position using acyl. The purpose of this work is to forecast the anticancer activity of alizarin and its derivatives on the MMP-9 receptor using. Important biological activity factors will be identified by Quantitative Structure Activity molecular docking Relationship (QSAR) and projected absorption, distribution, metabolism, elimination, and toxicity (ADMET). Using Molegro Virtual Docker (MVD), molecular docking was carried out on the MMP 9 receptor (4WZV.pdb). LogP, Etot, and MR are the physicochemical parameters that are examined in order to produce QSAR. Statistical Package for the Social Science (SPSS) was used for the QSAR analysis. The pkCSM was utilized to determine ADMET prediction. The acyl alizarin derivatives have a lower rerank score than alizarin, according to the docking results so that they are predicted to have more potent anticancer activity. The QSAR analysis's findings indicated that logP and Etot had the greatest effects on the alizarin compound's and its derivatives' activity. The results of the ADMET prediction indicate that acyl alizarin is less harmful and superior to alizarin. Research findings show that it is possible to synthesize acyl alizarin derivatives, especially alizarin octanoate, which will then be tested in vitro or in vivo to determine its anti-breast cancer activity and toxicity.
Keywords
About the authors
M. R. T. Alifiansyah
Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga
Author for correspondence.
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
M. A. Herdiansyah
Department of Biology, Faculty of Science and Technology, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
R. C. Pratiwi
Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
R. P. Pramesti
Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
N. W. Hafsyah
Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
A. P. Rania
Department of Pharmaceutical Science, Faculty of Pharmacy, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
Ju. E. R. P. Putra
Department of Biology, Faculty of Science and Technology, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
P. A. Cahyono
Department of Biology, Faculty of Science and Technology, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
. Litazkiyyah
Department of Biology, Faculty of Science and Technology, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
S. K. Muhammad
Department of Physics, Faculty of Science and Technology, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
A. A. A. Murtadlo
Department of Biology, Faculty of Science and Technology, Universitas Airlangga; Division of Research and Development, Jalan Tengah
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
V. D. Kharisma
Department of Biology, Faculty of Science and Technology, Universitas Airlangga; Division of Research and Development, Jalan Tengah
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
A. N. M. Ansori
Division of Research and Development, Jalan Tengah; Postgraduate School, Universitas Airlangga; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Airlangga 4–6, Surabaya, East Java, 60115
V. Jakhmola
Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Chakrata Rd, Prem Nagar, Dehradun, Uttarakhand, 248007
P. K. Ashok
Gyani Inder Singh Institute of Professional Studies
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Sinola, Dehradun, Uttarakhand, 248003
J. M. Kalra
School of Pharmaceutical Sciences, Shri Guru Ram Rai University
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Dehradun, Uttarakhand, 248001
H. Purnobasuki
Department of Biology, Faculty of Science and Technology, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
I. A. Pratiwi
Department of Biology, Faculty of Science and Technology, Universitas Airlangga
Email: ahmad.affan.ali-2023@fst.unair.ac.id
Jl. Mulyorejo, Kec. Mulyorejo, Surabaya, East Java, 60115
References
- Hanahan, D., Weinberg, R.A. (2000). The Hallmarks of Cancer. Cell, 100(1), 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
- Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A. et al. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209-249. https://doi.org/10.3322/caac.21660
- Yabluchanskiy, A, Ma, Y, Iyer, R.P., Hall, M.E., Lindsey, M.L. (2013). Matrix metalloproteinase-9: Many shades of function in cardiovascular disease. Physiology, 28(6), 391-403. https://doi.org/10.1152/physiol.00029.2013
- Greenlee, K.J., Corry, D.B., Engler, D.A., Matsunami, R.K., Tessier, P., Cooc, R.G. et al. (2006). Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation. The Journal of Immunoljgy, 177(10), 7312-7321. https://doi.org/10.4049/jimmunol.177.10.7312
- Khandia, R, Munjal, A. (2020). Interplay between inflammation and cancer. Chapter in a book: Advances in Protein Chemistry and Structural Biology, 119, 199-245. https://doi.org/10.1016/bs.apcsb.2019.09.004
- Kessenbrock, K., Plaks, V., Werb, Z. (2010). Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell, 141(1), 52-67. https://doi.org/10.1016/j.cell.2010.03.015
- Quintero-Fabian, S., Arreola, R., Becerril-Villanueva, E., Torres-Romero, J.C., Arana-Argae, V., Lara-Riegos, J. et al. (2019). Role of matrix metalloproteinases in angiogenesis and cancer. Frontiers in Oncology, 9, Article 1370. https://doi.org/10.3389/fonc.2019.01370
- Nelson, A. R., Fingleton, B., Rothenberg, M. L., Matrisian, L. M. (2000). Matrix metalloproteinases: Biologic activity and clinical implications. Journal of Clinical Oncology, 18(5), 1135-1149. https://doi.org/10.1200/jco.2000.18.5.1135
- Merdad, A., Karim, S., Schulten, H. J., Dallol, A., Buhmeida, A., Al-Thubaity, F. et al. (2014). Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis. Anticancer Research, 34(3), 1355-1366.
- Meng, Q., Liang, C., Hua, J., Zhang, B., Liu, J., Zhang, Y. et al. (2020). A miR-146a-5p/TRAF6/NF-kB p65 axis regulates pancreatic cancer chemoresistance: functional validation and clinical significance. Theranostics, 10(9), 3967-3979. https://doi.org/10.7150/thno.40566
- Li, K., Zhang, Z., Mei, Y., Yang, Q., Qiao, S., Ni, C. et al. (2021). Metallothionein-1G suppresses pancreatic cancer cell stemness by limiting activin A secretion NF-KB inhibition. Theranostics, 11(7), 3196-2212. https://doi.org/10.7150/thno.51976
- Lindenmeyer, F., Legrand, Y., Menashi, S. (1997). Upregulation of MMP-9 expression in MDA-MB231 tumor cells by platelet granular membrane. FEBS Letters, 418(1-2), 19-22. https://doi.org/10.1016/s0014-5793(97)01336-7
- Mishra, S. R., Nandhakumar, P., Yadav, K. P., Barik, S., Kumar, A., Saini, M. et al. (2017). In vitro analysis of alizarin as novel therapeutic agent for murine breast cancer. The Pharma Innovation Journal, 6(10), 345-350.
- Ekowati, J., Diyah, N. W., Nofianti, K. A., Hamid, I. S., Siswandono (2018). Mo-lecular Docking of Ferulic Acid Derivatives on P2Y12 Receptor and their ADMET Prediction. Journal of Mathematical and Fundamental Sciences, 50(2), 203-219. https://doi.org/10.5614/j.math.fund.sci.2018.50.2.8
- Kamath, V., Pai, A. (2017). Application of molecular descriptors in modern computational drug design-an overview. Research Journal of Pharmacy and Technology, 10(9), 3237-3241. http://doi.org/10.5958/0974-360X.2017.00574.1
- Habeela, J.N., Maruga, R.M.K.M. (2018). In silico molecular docking studies on the chemical constituents of clerodendrum phlomidis for its cytotoxic potential against breast cancer markers. Research Journal of Pharmacy and Technology, 11(4), Article 1612-1618. http://doi.org/10.5958/0974-360X.2018.00300.1
- Hardjono, S. (2012). Modification of the structure of 1 — (benzoyloxy) ureaand quantitative relationship of its structure-cytotoxic activity. Author's abstract of the thesis. Universitas Airlangga, Indonesia, 2012. (In Indonesian)
- Hardjono, S., Siswodihardjo, S., Pramono, P., Darmanto, W. (2016). Quantitative structure-cytotoxic activity relationship 1-(benzoyloxy) urea and its derivative. Current Drug Discovery Technologies, 13(2), 101-108. https://doi.org/10.2174%2F1570163813666160525112327
- Pinzi, L., Rastelli, G. (2019). Molecular docking: Shifting paradigms in drug discovery. International Journal of Molecular Sciences, 20(18), Article 4331. https://doi.org/10.3390/ijms2018433
- Park, K. D., Lee, S. G., Kim, S. U., Kim, S. H., Sun, W. S., Cho, S. J. et al. (2004). Anticancer activity of 3-O-acyl and alkyl-(-)-epicatechin derivatives. Bioorganic and Medicinal Chemistry Letters, 14(20), 5189-5192. https://doi.org/10.1016/j.bmcl.2004.07.063
- Hoque, I., Chatterjee, A., Bhattacharya, S., Biswas, R. (2017). An approach of computer-aided drug design (CADD) tools for in silico pharmaceutical drug design and development. International Journal of Advanced Research in Biological Sciences, 4(2), 60-71. http://doi.org/10.22192/ijarbs.2017.04.02.009
- Abdel-Ilah, L., Veljovic, E., Gurbeta, L., Badnjevic, A. (2017). Applications of QSAR study in drug design. International Journal of Engineering Research and Technology (IJERT), Vol. 6(6), 582-587.
- Verma, J., Khedkar, V. M., Coutinho, E. C. (2010). 3D-QSAR in drug design-a review. Current Topics in Medicinal Chemistry, 10(1), 95-115. https://doi.org/10.2174/156802610790232260
- Pathan, S., Ali, S. M., Shrivastava, M. (2016). Quantitative structure activity relationship and drug design: A review. International Journal of Research in Biosciences, 5(4), 1-5.
- Pires, D. E. V., Blundell, T. L., Ascher, D. B. (2015). pkCSM: Predicting small-mol-ecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066-4072. https://doi.org/10.1021/acs.jmedchem.5b00104
- Pagadala, N. S., Syed, K., Tuszynski, J. (2017). Software for molecular docking: A review. Biophysical Reviews, 9(2), 91-102. https://doi.org/10.1007/s12551-016-0247-1
- Ramirez, D., Caballero, J. (2018). Is it reliable to take the molecular docking top scoring position as the best solution without considering available structural data? Molecules, 23(5), Article 1038. https://doi.org/10.3390/molecules23051038
- Patlewicz, G., Jeliazkova, N., Safford, R. J., Worth, A. P., Aleksiev, B. (2008). An evaluation of the implementation of the Cramer classification scheme in the Toxtree software. SAR and QSAR in Environmental Researc, 19(5-6), 495-524. https://doi.org/10.1080/10629360802083871
- McMurry, J., E., Fay, R., C. (2012). Chemistry. Boston: Prentice Hall, 2012.
- Klebe, G. (2013). Protein-Ligand Interactions as the Basis for Drug Action. Chapter in a book: Drug Design. Springer, Berlin, Heidelberg, 2013. https://doi.org/10.1007/978-3-642-17907-5_4
- Grogan, S, Preuss, C.V. (2023). Pharmacokinetics. Chapter in a book: StatPearls [Internet]. StatPearls Publishing LLC., 2023.
- Paul, A. (2019). Drug Absorption and Bioavailability. Chapter in a book: Introduction to Basics of Pharmacology and Toxicology. Springer, Singapore, 2019. https://doi.org/10.1007/978-981-32-9779-1
- Chevillard, F., Lagorce, D., Reynes, C., Villoutreix, B. O., Vayer, P., Miteva, M. A. (2012). In silico prediction of aqueous solubility: A multimodel protocol based on chemical similarity. Molecular Pharmaceutics, 9(11), 3127-3135. https://doi.org/10.1021/mp300234q
- Gleeson, M. P. (2008). Generation of a set of simple, interpretable ADMET rules of thumb. Journal of Medicinal Chemistry, 51(4), 817-834. https://doi.org/10.1021/jm701122q
- Currie, G. M. (2018). Pharmacology, part 2: Introduction to pharmacokinetics. Journal of Nuclear Medicine Technology, 46(3), 221-230. https://doi.org/10.2967/jnmt.117.199638
- Smith, D. A., Beaumont, K., Maurer, T. S., Di, L. (2015). Volume of distribution in drug design. Miniperspective. Journal of Medicinal Chemistry, 58(15), 5691-5698. https://doi.org/10.1021/acs.jmedchem.5b00201
- Jeffrey, P., Summerfield, S. (2010). Assessment of the blood-brain barrier in CNS drug discovery. Neurobiology of Disease, 37(1), 33-37. https://doi.org/10.1016/j.nbd.2009.07.033
- Wilde, M., Pichini, S., Pacifici, R., Tagliabracci, A., Busardo, F. P., Auwarter, V. et al. (2019). Metabolic Pathways and Potencies of New Fentanyl Analogs. Frontiers in pharmacology, 10, Article 238. https://doi.org/10.3389%2Ffphar.2019.00238
- Rizzieri, D., Paul, B., Kang, Y. (2019). Metabolic alterations and the potential for targeting metabolic pathways in the treatment of multiple myeloma. Journal of Cancer Metastasis and Treatment, 5, 26. https://doi.org/10.20517/2394-4722.2019.05
- Garza, A. Z., Park, S. B., Kocz, R. (2023). Drug Elimination. Chapter in a book: StatPearls [Internet]. StatPearls Publishing LLC., 2023.
- Herdiansyah, M. A., Ansori, A. N. M., Kharisma V. D., Alifiansyah, M. R. T., Anggraini, D., Priyono, Q. A. P., Yusniasari, P. A., Fetty, A. J. T., Zainul, R., Rebezov, M., Kolesnik, E., Maksimiuk, N. (2024). In silico study of cladosporol and its acyl derivatives as anti-breast cancer against alpha-estrogen receptor. Biosaintifika, 15(1), 1-13.
- Zainul, R., Kharisma, V. D., Ciuputri, P., Ansori, A. N. M., Herdiansyah, M. A., Sahadewa, S., Durry, F. D. (2024). Antiretroviral activity from elderberry (Sambucus nigra L.) flowers against HIV-2 infection via reverse transcriptase inhibition: A viroinformatics study. Healthcare in Low-resource Settings, 1(2024), 1-12. https://doi.org/10.4081/hls.2024.12047
- Krihariyani, D., Haryanto, E., Sasongkowati, R. (2021). in silico analysis of antiviral activity and pharmacokinetic prediction of brazilein sappan wood (Caesalpinia sappan L.) against SARS-CoV-2 spike glycoproteins. Indonesian Journal of Medical Laboratory Science and Technology, 3(1), 26-37. https://doi.org/10.33086/ijmlst.v3i1.1854
Supplementary files
