Analisis Sifat Mirip Obat, Prediksi ADMET, dan Penambatan Molekular Isatinil-2-Aminobenzoilhidrazon dan kompleks logam transisi Co(II), Ni(II), Cu(II), Zn(II) Terhadap BCL2-XL
Abstract
This article reports an drug-likeness analysis, ADMET profile, and molecular docking of isatinyl-2-aminobenzoylhydrazone (ISABH) and its transition metals Co(II), Ni(II), Cu(II), and Zn(II) complexes. SwissADME analysis for drug-likeness indicated that ISABH and Ni-ISABH met all parameters of the Lipinski rule. These compounds also showed good pharmacological criteria by admetSAR for their ADMET prediction. The molecular docking of all compounds against the main regulatory protein for apoptosis BCL-2 (PDB code: 2W3L) revealed that they well-interacted with the protein expressed by binding affinity of -6.1, -8.3; -8.3; -7.5; and -8.5 kcal/mol for ISABH, Cu-ISABH, Co-ISABH, Ni-ISABH, and Zn-ISABH, respectively.
Keywords
Full Text:
Full TextReferences
Z. Zhong, Z. Zhong, R. Xing, P. Li, and G. Mo, “The preparation and antioxidant activity of 2-[phenylhydrazine (or hydrazine)-thiosemicarbazone] chitosan,” Int. J. Biol. Macromol., vol. 47, no. 2, pp. 93-97, 2010.
P. Pedrosa, A. Carvalho, P. V. Baptista, and A. R. Fernandes, “Inorganic Coordination Chemistry: Where We Stand in Cancer Treatment?,” United Kingdom: IntechOpen Ltd., 2018.
A. K. El-Sawaf, F. El-Essawy, A. A. Nassar, and E. A. El-Samanody, “Synthesis, spectral, thermal and antimicrobial on cobalt(II), nickel(II), copper(II), zinc(II) and palladium(II) complexes containing thiosemicarbazone ligand,” J. Mol. Struct., vol. 1157, no. 2018, pp. 381-394, 2018.
F. El-Saied, B. El-Aarag, T. Salem, G. Said, S. A. M. Khalifa, and H. R. El-Seedi, “Synthesis, characterization, and in vivo anti-cancer activity of new metal complexes derived from isatin-N-(4)-antipyrine thiosemicarbazone ligand againts ehrlich ascites carcinoma cells,” Molecules, vol. 24, no. 18, pp. 1-25, 2019.
F. Martak, N. E. Safitri, E. M. M. Putri, A. B. Pambudi, and A. Fadlan, “Synthesis and anticancer study of complex nickel(II) 5,7-dibromoisatin-derived hydrazine carbothioamide,” AIP Conf. Proc., vol. 2237, no. 1, pp. 020082, 2020.
B. Bhrigu, D. Pathak, N. Siddiqui, M. S. Alam, and W. Ahsan, “Search for biological active isatins: A short review,” Int. J. Pharm. Sci. Drug Res., vol. 2, no. 4, pp. 229-235, 2010.
J. F. M. da Silva, S. J. Garden and A. Pinto, “The chemistry of isatins: A review from 1975 to 1999,” J. Braz. Chem. Soc., vol. 12, no. 3, pp. 273-324, 2001.
A. S. Grewal, “Isatin derivatives with several biological activities: A review,” Int. J. Pharm. Res., vol. 6, no. 1, pp. 1-7, 2014.
A. Q. Ali, S. G. Teoh, N. E. Eltayeb, M. B. K. Ahamed, and A. A. Majid, “Synthesis of nickel(II) complexes of isatin thiosemicarbazone derivatives: in vitro anti-cancer, DNA binding, and cleavage activities,” J. Coord. Chem., vol. 67, no. 20, pp. 3380-3400, 2014.
M. C. Rodrigues-Arguelles, M. B. Ferrari, F. Bisceglie, C. Pelizzi, G. Pelosi, S. Pinelli, M. Sassi, “Synthesis, characterization and biological activity of Ni, Cu and Zn complexes of isatin hydrazones,” J. Inorg. Biochem., vol. 98, no. 2, pp. 313-321, 2004.
E. Krovat, T. Steindl, and T. Langer, “Recent Advances in Docking and Scoring,” Curr. Comput.Aided Drug Des., vol. I, no. 1, pp. 93-102, 2005.
T. Nogrady, D. F. Weaver, “Medicinal Chemistry: A Molecular and Biochemical Approach,” New York: Oxford University Press, 2005.
J. L. Velázquez-Libera, F. Durán-Verdugo, A. Valdés-Jiménez, G. Núñez-Vivanco, and J. Caballero, “LigRMSD: A web server for automatic structure matching and RMSD calculations among identical and similar compounds in protein-ligand docking,’ Bioinformatics, vol. 36, no. 9, pp. 2912–2914, 2020.
K. Sargsyan, C. Grauffel, and C. Lim, “How molecular size impacts RMSD applications in molecular dynamics simulations,” J. Chem. Theory Comput., vol. 13, no. 4, pp. 1518–1524, 2017.
J. Kalita, D. Chetia, and M. Rudrapal, “Molecular docking, drug-likeness studies and ADMET prediction of quinoline imines for antimalarial activity,” J. Med. Chem. Drug Des., vol. 2, no. 1, pp. 1-7, 2019.
R. S. Hunoor, B. R. Patil, D. S. Badiger, V. M. Chandrasekar, I. S. Muchchandi, and K. B. Gudasi, "Co(II), Ni(II), Cu(II), and Zn(II) complexes of isatinyl-2-aminobenzoylhydrazone:synthesis, characterization and anticancer activity," Appl. Organometal. Chem. vol. 29, no. 2, pp. 101-108, 2014.
C. A. Lipinski, “Drug-like properties and the causes of poor solubility and poor permeability,” J. Pharmacol. Toxicol. Methods, vol. 44, no. 1, pp. 235–249, 2000.
J. Porter, A. Payne, B. De Candole, D. ford, B. Hutchinson, G. Trevitt, J. turner, C. Edwards, C. Watkins, I. Whitcombe, J. Davis, C. Stubberfield, “Tetrahydroisoquinoline amide substituted phenyl pyrazoles as selective Bcl-2 inhibitors,” Bioorganic Med. Chem. Lett., vol. 19, no. 1, pp. 230–233, 2009.
H. Berman, K. Henrick, H. Nakamura, and J. L. Markley, “The worldwide Protein Data Bank (wwPDB): Ensuring a single, uniform archive of PDB data,” Nucleic Acids Res., vol. 35, no. SUPPL. 1, pp. 2006–2008, 2007.
ChemAxon, “MarvinSketch.” ChemAxon, 2020, [Online]. Available: www.chemaxon.com
Schrödinger LLC, “The PyMOL Molecular Graphics System.” Schrödinger, LLC, New York, NY, Nov. 2015, [Online]. Available: http://www.pymol.org
O. Trott and A. J. Olson, “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading,” J. Comput. Chem., vol. 31, no. 2, pp. 455–461, Jan. 2009.
S. Dallakyan and A. J. Olson, “Small-Molecule Library Screening by Docking with PyRx,” in Chemical Biology: Methods in Molecular Biology, vol. 1263, J. E. Hempel, C. H. Williams, and C. C. Hong, Eds. New York, NY: Springer New York, 2015, pp. 243–250
H. Yang et al., “AdmetSAR 2.0: Web-service for prediction and optimization of chemical ADMET properties,” Bioinformatics, vol. 35, no. 6, pp. 1067–1069, 2019.
A. Daina, O. Michielin, and V. Zoete, “SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules,” Sci. Rep., vol. 7, no. October 2016, pp. 1–13, 2017.
W. J. Allen and R. C. Rizzo, “Implementation of the Hungarian algorithm to account for ligand symmetry and similarity in structure-based design,” J. Chem. Inf. Model., vol. 54, no. 2, pp. 518–529, 2014.
R. Daneman and A. Prat, “The blood-brain barrier,” Cold Spring Harb. Perspect. Biol., vol. 7, no. 1, pp. a020412–a020412, 2015.
T. Bohnert and L. S. Gan, “Plasma protein binding: From discovery to development,” J. Pharm. Sci., vol. 102, no. 9, pp. 2953–2994, 2013.
DOI: http://dx.doi.org/10.12962/j25493736.v5i2.7881
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.