DFT Study, POM Analyses and Molecular Docking of Novel Oxazaphosphinanes: Identification of Antifungal Pharmacophore Site

https://doi.org/10.22146/ijc.46375

Khadidja Otmane Rachedi(1), Rania Bahadi(2), Mohamed Aissaoui(3), Taibi Ben Hadda(4), Billel Belhani(5), Abdeslem Bouzina(6), Malika Berredjem(7*)

(1) Laboratory of Applied Organic Chemistry LCOA, Synthesis of Biomolecules and Molecular Modeling Group, Badji-Mokhtar - Annaba University, Box 12, 23000 Annaba, Algeria
(2) Laboratory of Applied Organic Chemistry LCOA, Synthesis of Biomolecules and Molecular Modeling Group, Badji-Mokhtar - Annaba University, Box 12, 23000 Annaba, Algeria
(3) Laboratory of Applied Organic Chemistry LCOA, Synthesis of Biomolecules and Molecular Modeling Group, Badji-Mokhtar - Annaba University, Box 12, 23000 Annaba, Algeria
(4) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah Almukkarramah, Saudi Arabia
(5) Laboratory of Applied Organic Chemistry LCOA, Synthesis of Biomolecules and Molecular Modeling Group, Badji-Mokhtar - Annaba University, Box 12, 23000 Annaba, Algeria
(6) Laboratory of Applied Organic Chemistry LCOA, Synthesis of Biomolecules and Molecular Modeling Group, Badji-Mokhtar - Annaba University, Box 12, 23000 Annaba, Algeria
(7) Laboratory of Applied Organic Chemistry LCOA, Synthesis of Biomolecules and Molecular Modeling Group, Badji-Mokhtar - Annaba University, Box 12, 23000 Annaba, Algeria
(*) Corresponding Author

Abstract


A computational Petra/Osiris/Molinspiration/DFT(POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of series of oxazaphosphinanes derivatives 1a-1f containing potential antifungal O,N-pharmacophore. Molecular docking study was performed in order to evaluate synthesized compounds their possible antifungal properties and their interactions in the binding site. Molecular docking studies revealed that the compounds 1a-1f have the potential to become lead molecules in the drug discovery process. The six compounds 1a1f analyzed here were previously synthesized by our group.

Keywords


oxazaphosphinane; DFT; Petra/Osiris/Molinspiration (POM) analyses; molecular docking

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References

[1] Masao, C., Kunitomo, A., Yoshihito, T., Kunio, S., Hirofumi, M., Ayumi, T., and Masatoshi, K., 2005, Phosphinane compounds with immunomodulating activity, PAT: WO2005014603.

[2] Zhang, H., Tsukuhara, R., Tigyi, G., and Prestwich, G.D., 2006, Synthesis of cyclic phosphonate analogues of (lyso)phosphatidic acid using a ring-closing metathesis reaction, J. Org. Chem., 71 (16), 6061–6066.

[3] Babouri, R., Rolland, M., Sainte-Catherine, O., Kabouche, Z., Lecouvey, M., Bakalara, N., Volle, J.N., Virieux, D., and Pirat, J.L., 2015, α-Halogenated oxaphosphinanes: Synthesis, unexpected reactions, and evaluation as inhibitors of cancer cell proliferation, Eur. J. Med. Chem., 104, 33-41.

[4] Hewitt, D.G., and Newland, G.L., 1977, Organophosphorus compounds. P-Arylated perhydro-1,2-azaphosphorines, Aust. J. Chem., 30 (3), 579–587.

[5] Shipov, A.E., Genkina, G.K., Petrovskii, P.V., Goryunov, E.I., and Makarov, M.V., 2011, Novel biologically active 1,3,2-oxazaphosphinane derivatives, Phosphorus Sulfur Silicon Relat. Elem., 186 (4), 945–951.

[6] Gilard, V., Martino, R., Malet-Martino, M., Niemeyer, U., and Pohl, J., 1999, Chemical stability and fate of the cytostatic drug ifosfamide and its N-dichloroethylated metabolites in acidic aqueous solutions, J. Med. Chem., 42 (14), 2542–2560.

[7] Volle, J.N., Kaloyanov, N., Saada, M.C., Virieux, D., and Pirat, J.L., 2007, Phosphinyl analogues of hydroxybupropion: (±)-2-aryl-3,3,5,5-tetramethyl-[1,4,2]-oxazaphosphinanes, Tetrahedron Lett., 48 (27), 4695–4697.

[8] Silverman, R.B., 2004, The Organic Chemistry of Drug Design and Drug Action, 2nd Ed., Academic Press, Burlington, Massachusetts.

[9] Tarakeshwar, P, Kim, D, Lee, H.M., Suh, S.B., and Kim, K.S., 2004, “Theoretical approaches to the design of functional nanomaterials” in Computational Materials Science, Vol. 15, Eds. Leszczynski, J., Elsevier B.V., Amsterdam, Netherlands, 119–170.

[10] Lakshmanan, A., McBrien, A., Zhang, J., and Dhole, V., 2014, Transformation of process engineering – A software perspective, Comput. Aided Chem. Eng., 34, 186–195.

[11] Fleming, I., 2010, Molecular Orbitals and Organic Chemical Reactions–Reference Edition, John Wiley & Sons, Chichester, United Kingdom.

[12] Boufas, W., Dupont, N., Berredjem, M., Berrezag, K., Becheker, I., Berredjem, H., and Aouf, N.E., 2014, Synthesis and antibacterial activity of sulfonamides. SAR and DFT studies, J. Mol. Struct., 1074, 180–185.

[13] Cheloufi, H., Bechlem, K., Boufas, W., Barbey, C., Bouzina, A., Belhani, B., Dupont, N., Aouf, N.E., and Berredjem, M., 2017, Synthesis, X-ray crystallographic and DFT studies of two new N-acylsulfonamides, J. Mater. Environ. Sci., 8 (3), 997–1003.

[14] Rachedi, K.O., Ouk, T.S., Bahadi, R., Bouzina, A., Djouad, S.E., Bechlem, K., Zerrouki, R., Ben Hadda, T., Almalki, F., and Berredjem, M., 2019, Synthesis, DFT and POM analyses of cytotoxicity activity of α-amidophosphonates derivatives: Identification of potential antiviral O,O-pharmacophore site, J. Mol. Struct., 1197, 196–203.

[15] Schuster, I., Koch, A., Heydenreich, M., Kleinpeter, E., Lázár, L., and Fülöp, F., 2008, Synthesis and conformational analysis of phenyl-substituted 1,3,2-oxazaphosphino[4,3-a]- and 1,2,3-oxathiazino[4,3-a]isoquinolines, J. Mol. Struct., 888 (1-3), 124–137.

[16] Cristau, H.J., Pirat, J.L., Virieux, D., Monbrun, J., Ciptadi, C., and Bekro, Y.A., 2005, Synthesis, reactivity and stereochemistry of new phosphorus heterocycles with 5- or 6-membered rings, J. Organomet. Chem., 690 (10), 2472–2481.

[17] Belhani, B., Bouzina, A., Berredjem, M., and Aouf, N.E., 2015, One-pot synthesis of novel oxazaphosphinanes under ultrasound irradiation and solvent-free conditions, Monatsh. Chem., 146 (11), 1871–1875.

[18] Lee, C., Yang, W., and Parr, R.G., 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.

[19] Organic Chemistry Portal, 2012, http://www.organic-chemistry.org/prog/peo/, accessed on 15 January 2016.

[20] Lourenço, A.L.P.G., Vegi, P.F., Faria, J.V., Pinto, G.S.P., dos Santos, M.S., Sathler, P.C., Saito, M.S., Santana, M., Dutra, T.P.P., Rodrigues, C.R., Monteiro, R.Q., Bernardino, A.M.R., and Castro, H.C., 2019, Pyrazolyl-tetrazoles and imidazolyl-pyrazoles as potential anticoagulants and their integrated multiplex analysis virtual screening, J. Braz. Chem. Soc.,30 (1) , 33–47.

[21] DesJarlais, R.L., Sheridan, R.P., Seibel, G.L., Dixon, J.S., Kuntz, I.D., and Venkataraghavan, R., 1988, Using shape complementarity as an initial screen in designing ligands for a receptor binding site of known three-dimensional structure, J. Med. Chem., 31 (4), 722–729.

[22] Kuntz, I.D., 1992, Structure-based strategies for drug design and discovery, Science, 257 (5073), 1078–1082.

[23] Mukherjee, S., Balius, T.E., and Rizzo, R.C., 2010, Docking validation resources: Protein family and ligand flexibility experiments, J. Chem. Inf. Model., 50 (11), 1986–2000.

[24] Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., Nakatsuji, H., Li, X., Caricato, M., Marenich, A., Bloino, J., Janesko, B.G., Gomperts, R., Mennucci, B., Hratchian, H.P., Ortiz, J.V., Izmaylov, A.F., Sonnenberg, J.L., Williams-Young, D., Ding, F., Lipparini, F., Egidi, F., Goings, J., Peng, B., Petrone, A., Henderson, T., Ranasinghe, D., Zakrzewski, V.G., Gao, J., Rega, N., Zheng, G., Liang, W., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Throssell, K., Montgomery, J.A., Jr., Peralta, J.E., Ogliaro, F., Bearpark, M., Heyd, J.J., Brothers, E., Kudin, K.N., Staroverov, V.N., Keith, T., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Millam, J.M., Klene, M., Adamo, C., Cammi, R., Ochterski, J.W., Martin, R.L., Morokuma, K., Farkas, O., Foresman, J.B., and Fox, D.J., 2016, Gaussian 09, Revision A.02, Gaussian 09 Inc., Wallingford CT.

[25] Becke. A.D., 1993, Density-functional thermochemistry. III. The role of exact exchange, J. Chem. Phys., 98 (7), 5648–5652.

[26] Francl, M.M., Pietro, W.J., Hehre, W.J., Binkley, J.S., Gordon, M.S., DeFrees, D.J., and Pople, J.A., 1982, Self-consistent molecular orbital methods. XXIII. A polarization-type basis set for second-row elements, J. Chem. Phys., 77 (7), 3654–3665.

[27] Pauling, L., 1932, The nature of the chemical bond. IV. The energy of single bonds and the relative electronegativity of atoms, J. Am. Chem. Soc., 54 (9), 3570–3582.

[28] Pearson, R.G., 2005, Chemical hardness and density functional theory, J. Chem. Sci., 117 (5), 369–377.

[29] Parr, R.G., Szentpály, L.V., and Liu, S., 1999, Electrophilicity index, J. Am. Chem. Soc., 121 (9), 1922–1924.

[30] Mabkhot, Y.N., Alatibi, F., El-Sayed, N., Al-Showiman, S., Kheder, N.A., Wadood, A., Rauf, A., Bawazeer, S., and Ben Hadda, T.B., 2016, Antimicrobial activity of some novel armedthiophenederivatives and petra/osiris/molinspiration (POM) analyses, Molecules, 21 (2), 222–238.

[31] Mabkhot, Y.N., Arfan, M., Zgou, H., Genc, Z.K., Genc, M., Rauf, A., Bawazeer, S., and Hadda, T.B., 2016, How to improve antifungal bioactivity: POM and DFT study of some chiral amides derivatives of diacetyl-L-tartaric acid and amines, Res. Chem. Intermed., 42 (12), 8055–8068.

[32] Sajid, Z., Ahmad, M., Aslam, S., Ashfaq, U.A., Zahoor, A.F., Saddique, F.A., Parvez, M., Hameed, A., Sultan, S., Zgou, H., and Hadda, T.B., 2016, Novel armed pyrazolobenzothiazine derivatives: Synthesis, X-Ray crystal structure and POM analyses of biological activity against drug resistant clinical isolate of Staphylococcus aureus, Pharm. Chem. J., 50 (3), 172–180.

[33] Ooms, F., 2000, Molecular modeling and computer aided drug design. Examples of their applications in medicinal chemistry, Curr. Med. Chem., 7 (2), 141–158.

[34] Shoichet, B.K., 2004, Virtual screening of chemical libraries, Nature, 432 (7019), 862–865.

[35] Jorgensen, W.L., 2004, The many roles of computation in drug discovery, Science, 303 (5665), 1813–1818.

[36] Aouad, M.R., Mayaba, M.M., Naqvi, A., Bardaweel, S.K., Al-Blewi, F.F., Messali, M., and Rezki, N., 2017, Design, synthesis, in silico and in vitro antimicrobial screenings of novel 1,2,4-triazoles carrying 1,2,3-triazole scaffold with lipophilic side chain tether, Chem. Cent. J., 11 (1), 117.

[37] Hashemi, S.M., Badali, H., Faramarzi, M.A., Samadi, N., Afsarian, M.H., Irannejad, H., and Emami, S., 2015, Novel triazole alcohol antifungals derived from fluconazole: Design, synthesis, and biological activity, Mol. Diversity, 19 (1), 15–27.

[38] Wu, J., Ni, T., Chai, X., Wang, T., Wang, H., Chen, J., Jin, Y., Zhang, D., Yu, S., and Jiang, Y., 2018, Molecular docking, design, synthesis and antifungal activity study of novel triazole derivatives, Eur. J. Med. Chem., 143, 1840–1846.

[39] Sastry, G.M., Adzhigirey, M., Day, T., Annabhimoju, R., and Sherman, W., 2013, Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments, J. Comput.-Aided Mol. Des., 27 (3), 221–234.

[40] O'Boyle, N.M., Banck, M., James, C.A., Morley, C., Vandermeersch, T., and Hutchison, G.R., 2011, Open Babel: An open chemical toolbox, J. Cheminf., 3, 33.

[41] Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R., and Ferrin, T.E., 1982, A geometric approach to macromolecule-ligand interactions, J. Mol. Biol.,161 (2), 269–288.



DOI: https://doi.org/10.22146/ijc.46375

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