Skip to main content
SpringerLink
Log in

Homology modelling, vHTS, pharmacophore, molecular docking and molecular dynamics studies for the identification of natural compound-derived inhibitor of MRP3 in acute leukaemia treatment

  • Original Paper
  • Published:
Chemical Papers Aims and scope Submit manuscript

Abstract

The pivotal role of MRP3 protein in acute leukaemia and the efficacy of natural compounds in cancer treatment have necessitated the current study to identify novel MRP3 inhibitors from natural source. The MRP3 protein was modelled and validated using well-accepted metrics, after which a validated multiple-ligand pharmacophore model (AHHHR_4) was built to screen natural compounds (n = 47,964). The combined pharmacophore screening with molecular docking was conducted to identify the hits drug-like compounds using ADMET profiling. The electronic behaviour of this set of compounds in gas phase was examined using density functional theory. Among the compounds (n = 7) with clean ADMET profile, NPC5486, which possessed the highest binding affinity with MRP3, was further subjected to 50 ns molecular dynamics (MD) simulation to understand its dynamics of binding. Analysis from the resulting MD simulation trajectories of NPC5486 in complex with the model protein alongside that of standard inhibitor (vincristine) showed not only the flexibility and interaction potential of the residues of the MRP3 with NPC5486 as indicated by the RMSF but also stability of the complex as indicated by the RMSD, RoG and number of hydrogen bonds of the ligand–protein complexes. Cluster analysis of the MD simulation trajectory files and dynamics-based MMGBSA computations further revealed that the observed interactions with important residues as well as the free energy contribution per residue were preserved in the dynamic environment. Overall, the current study has revealed drug-like compounds which can serve as potential inhibitors of MRP3 in the treatment of acute leukaemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14

Similar content being viewed by others

References

  • Akioka K, Masuda K, Harada S, Nakamura T, Okugawa K, Nakano K, Osaka Y, Tsuchiya K, Sako H (2013) Acute renal failure caused by hyperuremic acidemia in ABO-incompatible kidney transplant maintained with cyclosporine and high-dose mizoribine: A case report. Transplant Proc 45(7):2815–2818. https://doi.org/10.1016/j.transproceed.2013.03.052

    Article  CAS  PubMed  Google Scholar 

  • Ali I, Welch MA, Lu Y, Swaan PW, Brouwer KLR (2017) Identification of novel MRP3 inhibitors based on computational models and validation using an in vitro membrane vesicle assay. Eur J Pharm Sci 103:52–59. https://doi.org/10.1016/j.ejps.2017.02.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alyar S, Şen T, Özmen ÜÖ, Alyar H, Adem Ş, Şen C (2019) Synthesis, spectroscopic characterizations, enzyme inhibition, molecular docking study and DFT calculations of new Schiff bases of sulfa drugs. J Mol Struct 1185:416–424

    Article  CAS  Google Scholar 

  • Banerjee P, Eckert AO, Schrey AK, Preissner R (2018) ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 46(W1):W257–W263. https://doi.org/10.1093/nar/gky318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beck TC, Beck KR, Morningstar J, Benjamin MM, Norris RA (2021) Descriptors of cytochrome inhibitors and useful machine learning based methods for the design of safer drugs. Pharmaceuticals 14(5):472

    Article  CAS  Google Scholar 

  • Becke AD (1988) Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev A Gen Phys 38(6):3098–3100. https://doi.org/10.1103/physreva.38.3098

    Article  CAS  PubMed  Google Scholar 

  • Benkert P, Tosatto SCE, Schomburg D (2008) QMEAN: A comprehensive scoring function for model quality assessment. Proteins 71(1):261–277. https://doi.org/10.1002/prot.21715

    Article  CAS  PubMed  Google Scholar 

  • Berjanskii M, Zhou J, Liang Y, Lin G, Wishart DS (2012) Resolution-by-proxy: a simple measure for assessing and comparing the overall quality of NMR protein structures. J Biomol NMR 53(3):167–180

    Article  CAS  Google Scholar 

  • Bobrowska-Hägerstrand M, Lillås M, Mrówczyñska L, Wróbel A, Shirataki Y, Motohashi N, Hägerstrand H (2006) Resveratrol oligomers are potent MRP1 transport inhibitors. Anticancer Res 26(3A):2081–2084

    PubMed  Google Scholar 

  • Bochevarov AD, Harder E, Hughes TF, Greenwood JR, Braden DA, Philipp DM, Rinaldo D, Halls MD, Zhang J, Friesner RA (2013) Jaguar: A high-performance quantum chemistry software program with strengths in life and materials sciences. Int J Quantum Chem 113(18):2110–2142

    Article  CAS  Google Scholar 

  • Borst P, Evers R, Kool M, Wijnholds J (2000) A family of drug transporters: The multidrug resistance-associated proteins. J Natl Cancer Inst 92(16):1295–1302. https://doi.org/10.1093/jnci/92.16.1295

    Article  CAS  PubMed  Google Scholar 

  • Brooks BR, Brooks CL III, Mackerell AD Jr, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S (2009) CHARMM: the biomolecular simulation program. J Comput Chem 30(10):1545–1614

    Article  CAS  Google Scholar 

  • Case DA, Berryman J, Betz RM, Cerutti DS, Cheatham Iii TE, Darden TA, Duke RE, Giese TJ, Gohlke H, and Goetz AW (2015) AMBER 2015

  • Colovos C, Yeates TO (1993) Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci 2(9):1511–1519

    Article  CAS  Google Scholar 

  • Dalton JAR, Jackson RM (2007) An evaluation of automated homology modelling methods at low target–template sequence similarity. Bioinformatics 23(15):1901–1908

    Article  CAS  Google Scholar 

  • DeLano WL (2002) Pymol: An open-source molecular graphics tool. CCP4 Newsl Protein Crystallogr 40(1):82–92

  • De Vocht T, Buyck C, Deferm N, Qi B, Van Brantegem P, van Vlijmen H, Snoeys J, Hoeben E, Vermeulen A, Annaert P (2021) Identification of novel inhibitors of rat Mrp3. Eur J Pharm Sci 162:105813. https://doi.org/10.1016/j.ejps.2021.105813

    Article  CAS  PubMed  Google Scholar 

  • Elekofehinti OO, Iwaloye O, Olawale F, Chukwuemeka PO, Folorunso IM (2021) Newly designed compounds from scaffolds of known actives as inhibitors of survivin: computational analysis from the perspective of fragment-based drug design. Silico Pharmacol 9(1):47. https://doi.org/10.1007/s40203-021-00108-8

    Article  Google Scholar 

  • Fletcher JI, Williams RT, Henderson MJ, Norris MD, Haber M (2016) ABC transporters as mediators of drug resistance and contributors to cancer cell biology. Drug Resist Updat 26:1–9. https://doi.org/10.1016/j.drup.2016.03.001

    Article  PubMed  Google Scholar 

  • Fukushima-Uesaka H, Saito Y, Maekawa K, Hasegawa R, Suzuki K, Yanagawa T, Kajio H, Kuzuya N, Noda M, Yasuda K, Tohkin M, Sawada JI (2007) Genetic variations of the ABC transporter gene ABCC3 in a Japanese population. Drug Metab Pharmacokinet 22(2):129–135. https://doi.org/10.2133/dmpk.22.129

    Article  PubMed  Google Scholar 

  • Ghose AK, Viswanadhan VN, Wendoloski JJ (1998) Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods: an analysis of ALOGP and CLOGP methods. J Phys Chem A 102(21):3762–3772

    Article  CAS  Google Scholar 

  • Gilibili RR, Chatterjee S, Bagul P, Mosure KW, Murali BV, Mariappan TT, Mandlekar S, Lai Y (2017) Coproporphyrin-I: A fluorescent, endogenous optimal probe substrate for ABCC2 (MRP2) suitable for vesicle-based MRP2 inhibition assay. Drug Metab Dispos 45(6):604–611. https://doi.org/10.1124/dmd.116.074740

    Article  CAS  PubMed  Google Scholar 

  • Hagar M, Ahmed HA, Aljohani G, Alhaddad OA (2020) Investigation of some antiviral N-heterocycles as COVID 19 drug: molecular docking and DFT calculations. Int J Mol Sci 21(11):3922

    Article  CAS  Google Scholar 

  • Halgren TA (2009) Identifying and characterizing binding sites and assessing druggability. J Chem Inf Model 49(2):377–389. https://doi.org/10.1021/ci800324m

    Article  CAS  PubMed  Google Scholar 

  • Hollenstein K, Dawson RJP, Locher KP (2007) Structure and mechanism of ABC transporter proteins. Curr Opin Struct Biol 17(4):412–418

    Article  CAS  Google Scholar 

  • Howlader NNA, Krapcho M, Miller D, Bishop K, Kosary CL, and Yu M (2017) Cronin KA (eds). SEER Cancer Statistics Review, 1975–2014, National Cancer Institute. Bethesda, MD

  • Huang J, MacKerell ADJ (2013) CHARMM36 all-atom additive protein force field: validation based on comparison to NMR data. J Comput Chem 34(25):2135–2145. https://doi.org/10.1002/jcc.23354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwaloye O, Elekofehinti OO, Momoh AI, Babatomiwa K, Ariyo EO (2020) In silico molecular studies of natural compounds as possible anti-Alzheimer’s agents: ligand-based design. Netw Model Anal Heal Informatics Bioinforma. https://doi.org/10.1007/s13721-020-00262-7

    Article  Google Scholar 

  • Jiang L, He Y, Luo G, Yang Y, Li G, Zhang Y (2016) Discovery of potential novel microsomal triglyceride transfer protein inhibitors via virtual screening of pharmacophore modelling and molecular docking. Mol Simul 42(15):1223–1232

    Article  CAS  Google Scholar 

  • Jo S, Kim T, Iyer VG, Im W (2008) CHARMM-GUI: a web-based graphical user interface for CHARMM. J Comput Chem 29(11):1859–1865

    Article  CAS  Google Scholar 

  • Khalid M, Ullah MA, Adeel M, Khan MU, Tahir MN, Braga AAC (2019) Synthesis, crystal structure analysis, spectral IR, UV–Vis, NMR assessments, electronic and nonlinear optical properties of potent quinoline based derivatives: interplay of experimental and DFT study. J Saudi Chem Soc 23(5):546–560

    Article  CAS  Google Scholar 

  • Köck K, Ferslew BC, Netterberg I, Yang K, Urban TJ, Swaan PW, Stewart PW, Brouwer KLR (2014) Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters multidrug resistance-associated proteins 3 and 4. Drug Metab Dispos 42(4):665–674

    Article  Google Scholar 

  • Lauria A, Ippolito M, Fazzari M, Tutone M, Di Blasi F, Mingoia F, Almerico AM (2010) IKK-β inhibitors: An analysis of drug–receptor interaction by using molecular docking and pharmacophore 3D-QSAR approaches. J Mol Graph Model 29(1):72–81

    Article  CAS  Google Scholar 

  • Le M-T, Hoang V-N, Nguyen D-N, Bui T-H-L, Phan T-V, Huynh PN-H, Tran T-D, Thai K-M (2021) Structure-based discovery of ABCG2 Inhibitors: A homology protein-based pharmacophore modeling and molecular docking approach. Molecules 26(11):3115

    Article  CAS  Google Scholar 

  • Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter 37(2):785–789. https://doi.org/10.1103/physrevb.37.785

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Cheng X, Swails JM, Yeom MS, Eastman PK, Lemkul JA, Wei S, Buckner J, Jeong JC, Qi Y, Jo S, Pande VS, Case DA, Brooks CL, MacKerell AD, Klauda JB, Im W (2016) CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field. J Chem Theory Comput 12(1):405–413. https://doi.org/10.1021/acs.jctc.5b00935

    Article  CAS  PubMed  Google Scholar 

  • Lyne PD, Lamb ML, Saeh JC (2006) Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J Med Chem 49(16):4805–4808

    Article  CAS  Google Scholar 

  • Maynadié M (2015) Acute Leukemia. Rev Francoph Des Lab 2015(471):27–28. https://doi.org/10.1016/s1773-035x(15)30070-8

    Article  Google Scholar 

  • Miller BR, McGee TD, Swails JM, Homeyer N, Gohlke H, Roitberg AE (2012) MMPBSA.py: An efficient program for end-state free energy calculations. J Chem Theory Comput 8(9):3314–3321. https://doi.org/10.1021/ct300418h

    Article  CAS  PubMed  Google Scholar 

  • Noroozi-Aghideh A, Safavi A, Ghodousi ES, Rajaeinejad M, Moghaddam PT (2020) Homology modeling and molecular docking of hABCC3/MRP3 with chemotherapeutic agents in acute leukemia. Jundishapur J Nat Pharm Prod. https://doi.org/10.5812/jjnpp.69407

    Article  Google Scholar 

  • Olawale F, Iwaloye O, Elekofehinti OO (2021a) Virtual screening of natural compounds as selective inhibitors of polo-like kinase-1 at C-terminal polo box and N-terminal catalytic domain. J Biomol Struct Dyn. https://doi.org/10.1080/07391102.2021.1991476

    Article  PubMed  Google Scholar 

  • Olawale F, Olofinsan K, Iwaloye O, and Ologuntere TE (2021b). Phytochemicals from Nigerian medicinal plants modulate therapeutically-relevant diabetes targets: insight from computational direction. Adv Tradit Med 1–15

  • Olawale F, Olofinsan K, Iwaloye O, Chukwuemeka PO, Elekofehinti OO (2022) Screening of compounds from Nigerian antidiabetic plants as protein tyrosine phosphatase 1B inhibitor. Comput Toxicol 21:100200. https://doi.org/10.1016/j.comtox.2021.100200

    Article  Google Scholar 

  • Parthasarathi R, Subramanian V, Roy DR, Chattaraj PK (2004) Electrophilicity index as a possible descriptor of biological activity. Bioorg Med Chem 12(21):5533–5543

    Article  CAS  Google Scholar 

  • Remmert M, Biegert A, Hauser A, Söding J (2011) HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment. Nat Methods 9(2):173–175. https://doi.org/10.1038/nmeth.1818

    Article  CAS  PubMed  Google Scholar 

  • Salentin S, Schreiber S, Haupt VJ, Adasme MF, Schroeder M (2015) PLIP: Fully automated protein-ligand interaction profiler. Nucleic Acids Res 43(W1):W443–W447. https://doi.org/10.1093/nar/gkv315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saxena S, Abdullah M, Sriram D, Guruprasad L (2018) Discovery of novel inhibitors of Mycobacterium tuberculosis MurG: Homology modelling, structure based pharmacophore, molecular docking, and molecular dynamics simulations. J Biomol Struct Dyn 36(12):3184–3198

    Article  CAS  Google Scholar 

  • Scheffer GL, Kool M, de Haas M, de Vree JML, Pijnenborg ACLM, Bosman DK, Oude Elferink RPJ, Van Der Valk P, Borst P, Scheper RJ (2002) Tissue distribution and induction of human multidrug resistant protein 3. Lab Investig 82(2):193–201. https://doi.org/10.1038/labinvest.3780411

    Article  CAS  PubMed  Google Scholar 

  • Song XR, Zheng Y, He G, Yang L, Luo YF, He ZY, Li SZ, Li JM, Yu S, Luo X, Hou SX, Wei YQ (2010) Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma. J Pharm Sci 99(12):4874–4879. https://doi.org/10.1002/jps.22200

    Article  CAS  PubMed  Google Scholar 

  • Steinbach D, Legrand O (2007) ABC transporters and drug resistance in leukemia: Was P-gp nothing but the first head of the Hydra? Leukemia 21(6):1172–1176. https://doi.org/10.1038/sj.leu.2404692

    Article  CAS  PubMed  Google Scholar 

  • Studer G, Tauriello G, Bienert S, Biasini M, Johner N, Schwede T (2021) ProMod3 - A versatile homology modelling toolbox. PLoS Comput Biol 17(1):e1008667. https://doi.org/10.1371/JOURNAL.PCBI.1008667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tubiana T, Carvaillo J-C, Boulard Y, Bressanelli S (2018) TTClust: a versatile molecular simulation trajectory clustering program with graphical summaries. J Chem Inf Model 58(11):2178–2182

    Article  CAS  Google Scholar 

  • Uchiumi T, Hinoshita E, Haga S, Nakamura T, Tanaka T, Toh S, Furukawa M, Kawabe T, Wada M, Kagotani K, Okumura K, Kohno K, Akiyama SI, Kuwano M (1998) Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Biochem Biophys Res Commun 252(1):103–110. https://doi.org/10.1006/bbrc.1998.9546

    Article  CAS  PubMed  Google Scholar 

  • van de Velde ME, Kaspers GL, Abbink FCH, Wilhelm AJ, Ket JCF, van den Berg MH (2017) Vincristine-induced peripheral neuropathy in children with cancer: A systematic review. Crit Rev Oncol Hematol 114:114–130. https://doi.org/10.1016/j.critrevonc.2017.04.004

    Article  PubMed  Google Scholar 

  • Van Der Kolk DM, De Vries EGE, Noordhoek L, Van Den Berg E, Van Der Pol MA, Müller M, Vellenga E (2001) Activity and expression of the multidrug resistance proteins P-glycoprotein, MRP1, MRP2, MRP3 and MRP5 in de novo and relapsed acute myeloid leukemia. Leukemia 15(10):1544–1553. https://doi.org/10.1038/sj.leu.2402236

    Article  CAS  PubMed  Google Scholar 

  • Veber DF, Johnson SR, Cheng H-Y, Smith BR, Ward KW, Kopple KD (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45(12):2615–2623. https://doi.org/10.1021/jm020017n

    Article  CAS  PubMed  Google Scholar 

  • Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46(W1):W296–W303. https://doi.org/10.1093/nar/gky427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willard L, Ranjan A, Zhang H, Monzavi H, Boyko RF, Sykes BD, Wishart DS (2003) VADAR: a web server for quantitative evaluation of protein structure quality. Nucleic Acids Res 31(13):3316–3319

    Article  CAS  Google Scholar 

  • Wu CP, Calcagno AM, Hladky SB, Ambudkar SV, Barrand MA (2005) Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5). FEBS J 272(18):4725–4740. https://doi.org/10.1111/j.1742-4658.2005.04888.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye ZW, Camus S, Augustijns P, Annaert P (2010) Interaction of eight HIV protease inhibitors with the canalicular efflux transporter ABCC2 (MRP2) in sandwich-cultured rat and human hepatocytes. Biopharm Drug Dispos 31(2–3):178–188. https://doi.org/10.1002/bdd.701

    Article  CAS  PubMed  Google Scholar 

  • Yu W, He X, Vanommeslaeghe K, MacKerell ADJ (2012) Extension of the CHARMM General Force Field to sulfonyl-containing compounds and its utility in biomolecular simulations. J Comput Chem 33(31):2451–2468. https://doi.org/10.1002/jcc.23067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang YK, Wang YJ, Gupta P, Chen ZS (2015) Multidrug Resistance Proteins (MRPs) and Cancer Therapy. AAPS J 17(4):802–812. https://doi.org/10.1208/s12248-015-9757-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the technical support received from Computational Biologists at the Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.

Funding

This research received no external financial or non-financial supports.

Author information

Authors and Affiliations

  1. Nano-Gene and Drug Delivery Group, Department of Biochemistry, School of Life Science, University of Kwazulu Natal, Durban, 4000, South Africa

    Femi Olawale

  2. Department of Biochemistry, University of Lagos, Lagos, Nigeria

    Femi Olawale

  3. Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, P.M.B. 704, Akure, 360001, Ondo State, Nigeria

    Opeyemi Iwaloye

  4. Department of Biochemistry, Nile University of Nigeria, Jabi, Nigeria

    Kolawole Olofinsan

  5. Human Nutraceuticals and Bioinformatics Research Unit, Department of Biochemistry, Salem University, Lokoja, Nigeria

    Oludare M. Ogunyemi

  6. Department of Biochemistry, Faculty of Science and Technology, Bingham University, Karu, Nasarawa, Nigeria

    Gideon A. Gyebi

  7. Department of Biophysics, Faculty of Sciences, Cairo University, Giza, Egypt

    Ibrahim M. Ibrahim

Authors
  1. Femi Olawale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Opeyemi Iwaloye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kolawole Olofinsan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Oludare M. Ogunyemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gideon A. Gyebi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ibrahim M. Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

FO helped in project design, generation and analysis of data, interpretation of data, preparation of manuscript draft and approval of manuscript for submission. OI and OO performed data analysis, data interpretation, substantial manuscript revision and approval of manuscript for submission. KO was involved in manuscript draft, substantial manuscript revision and approval of manuscript for submission. II contributed to data acquisition, preparation of manuscript draft and approval of manuscript for submission. GG helped in substantial manuscript revision, project supervision and provision of resources for research and approval of manuscript for submission. All authors have read and approved the manuscript for submission.

Corresponding author

Correspondence to Femi Olawale.

Ethics declarations

Ethical approval

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 19007 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Olawale, F., Iwaloye, O., Olofinsan, K. et al. Homology modelling, vHTS, pharmacophore, molecular docking and molecular dynamics studies for the identification of natural compound-derived inhibitor of MRP3 in acute leukaemia treatment. Chem. Pap. 76, 3729–3757 (2022). https://doi.org/10.1007/s11696-022-02128-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11696-022-02128-w

Keywords

Search

Navigation