European Journal of Chemistry

Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study

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Published: Mar 31, 2015
DOI: https://doi.org/10.5155/eurjchem.6.1.1-7.1139
Keywords:
Steriods, Pregnenolone, Anti-HIV activity, Mitsunobu reaction, Molecular modeling study, 17α-Hydroxylase/C17, 20-lyase
Section
Research Article
Issue
Vol. 6 No. 1 (2015): March 2015
Dates
Received 2014-08-31
Accepted 2014-10-29
Published 2015-03-31


Main Article Content

Kuthair Mohammed Mahdi
Department of Chemistry, College of Education, University of Qadisiya, Qadisiya, 58002, Iraq
Nabeel Abed Abdul-Reda
Department of Chemistry, College of Education, University of Qadisiya, Qadisiya, 58002, Iraq
Najim Aboud Al-Masoudi
Department of Chemistry, College of Science, University of Basrah, Basrah, 61004, Iraq

Abstract

A new series of (5-pregnen-20-on-3α-yl)-substituted-benzoate analogues (10-13), (5-pregnene-20-on-3α-yl)-3-(substituted)acrylate derivatives (17-19) as well as the (17-(2-acetoxyacetyl)pregen-3α-yl)-3,4,5-trihydroxybenzoate (21) were synthesized from the β-pregenenolone scaffolds, by applying Mitsunobu reaction. All new compounds were characterized by 1H, 13C and 2D NMR spectroscopy. The inversion in configuration at C-3 during the formation of α-ester analogues was confirmed by NOESY NMR spectroscopy. The new compounds were evaluated for their in vitro antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells. Compounds 18 showed an EC50 value of >1.95 mg/mL. In addition, preliminary structure-activity relationship and molecular modeling of compound 18 has been studied.


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Mahdi, K. M.; Abdul-Reda, N. A.; Al-Masoudi, N. A. Exploration of New 3α-Pregnenolone Ester Analogues via Mitsunobu Reaction, Their Anti-HIV Activity and Molecular Modeling Study. Eur. J. Chem. 2015, 6, 1-7.

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References

[1]. Mensah-Nyagan, A. G.; Meyer, L.; Schaeffer, V.; Kibaly, C.; Patte-Mensah, C. Psychoneuroendocrino. 2009, 34, 169-177.
http://dx.doi.org/10.1016/j.psyneuen.2009.06.004

[2]. Ibrahim-Ouali, M. Steroids 2007, 72, 475-508.
http://dx.doi.org/10.1016/j.steroids.2007.03.004

[3]. Bhatti, H. N.; Khera, R. A. Steroids 2012, 77, 1267-1290.
http://dx.doi.org/10.1016/j.steroids.2012.07.018

[4]. Aggarwal, S.; Thareja, S.; Verma, A.; Bhardwaj, T. R.; Kumar, M. Steroids 2010, 75, 109-153.
http://dx.doi.org/10.1016/j.steroids.2009.10.005

[5]. Li, H. J.; Jiang, Y.; Li, P. Nat. Prod. Rep. 2006, 23, 735-752.
http://dx.doi.org/10.1039/b609306j

[6]. Ifere, G. O.; Barr, E.; Equan, A.; Gordon, K.; Singh, Chaudhany, J. J.; Igietseme, J. U.; Ananaba, G. A. Cancer Detect. Prev. 2009, 32, 319-328.
http://dx.doi.org/10.1016/j.cdp.2008.12.002

[7]. Bansal, R.; Guleria, S.; Thota, S.; Bodhankar, S. L.; Patwardhan, M. R.; Zimmer, C. Steroids 2012, 77, 621-629.
http://dx.doi.org/10.1016/j.steroids.2012.02.005

[8]. Dubey, R. K.; Oparil, S.; Imthurn, B.; Jackson, E. K. Cardiovasc. Res. 2002, 53, 688-708.
http://dx.doi.org/10.1016/S0008-6363(01)00527-2

[9]. Holst, J. P.; Soldin, S. J.; Tractenberg, R. E.; Guo, T.; Kundra, P.; Verbalis, J. G. Steroids 2007, 72, 71-84.
http://dx.doi.org/10.1016/j.steroids.2006.11.001

[10]. Auci, D. L.; Reading, C. L.; Frincke, J. M. Autoimmun Rev. 2009, 8, 369-372.
http://dx.doi.org/10.1016/j.autrev.2008.11.011

[11]. Jursic, B. S.; Upadhyay, S. K.; Creech, C. C.; Neumann, D. M. Bioorg. Med. Chem. Lett. 2010, 20, 7372-7375.
http://dx.doi.org/10.1016/j.bmcl.2010.10.044

[12]. Banday, A. H.; Iqbal, Z. M.; Ganaie, B. A. Steroids 2011, 76, 1358-1362.
http://dx.doi.org/10.1016/j.steroids.2011.07.001

[13]. Billich, A.; Nussbaumer, P.; Lehr, P. J. Steroid Biochem. 2000, 73, 225-235.
http://dx.doi.org/10.1016/S0960-0760(00)00077-7

[14]. Saha, P.; Fortin, S.; Leblanc, V.; Parent, S.; Asselin, E.; Berube, G. Steroids 2012, 77, 1113-1122.
http://dx.doi.org/10.1016/j.steroids.2012.06.004

[15]. Bansal, R.; Guleria, S.; Thota, S.; Hartmann, R. W.; Zimmer, C. Chem. Pharma. Bull. 2011, 59, 327-331.
http://dx.doi.org/10.1248/cpb.59.327

[16]. Gauthier, S.; Martel, C.; Labrie, F. J. Steroid Biochem. 2012, 132, 93-104.
http://dx.doi.org/10.1016/j.jsbmb.2012.02.006

[17]. Sheridan, P. J.; Blum, K.; Trachtenberg, M. C. Steroid receptors and disease: cancer, autoimmune, bone, and circulatory disorders, Marcel Dekker Inc., 1988, pp. 289-564.

[18]. Reddz, D. S. Prog. Brain Res. 2010, 186, 113-137.
http://dx.doi.org/10.1016/B978-0-444-53630-3.00008-7

[19]. Aird, R. B. J. Nerv. Mental Dis. 1944, 99, 501-510.
http://dx.doi.org/10.1097/00005053-194405000-00005

[20]. Aird, R. B.; Gordan, G. S. J. Am. Med. Assoc. 1951, 145, 715-719.
http://dx.doi.org/10.1001/jama.1951.02920280027006

[21]. Gyermek, L.; Genther, G.; Fleming, N. Intern. J. Neuropharm. 1967, 6, 191-198.
http://dx.doi.org/10.1016/0028-3908(67)90005-6

[22]. Green, C. J.; Halsey, M. J.; Precious, S.; Wardley-Smith, B. Lab. Animals 1978, 12, 85-89.
http://dx.doi.org/10.1258/002367778780953206

[23]. Moffat, L. E.; Kirk, D.; Tolley, D. A.; Smith, M. F.; Beastall, G. British J. Urology 1988, 61, 439-440.
http://dx.doi.org/10.1111/j.1464-410X.1988.tb06593.x

[24]. Mahler, C.; Verhelst, J.; Denis, L. Cancer 1993, 71, 1068-1073.
http://dx.doi.org/10.1002/1097-0142(19930201)71:3+<1068::AID-CNCR2820711427>3.0.CO;2-5

[25]. Lake-Bakaar, G.; Scheuer, P. J.; Sherlock, S. British Med. J. 1987, 294, 419-442.
http://dx.doi.org/10.1136/bmj.294.6569.419

[26]. Njar, V. C.; . Klus, G. T.; Brodie, A. M. H. Bioorg. Med. Chem. Lett. 1996, 6, 2777-2782.
http://dx.doi.org/10.1016/S0960-894X(96)00512-4

[27]. Njar, V. C.; Kato, K.; Nnane, I. P.; Grigoryev, D. N.; Long, B. J.; Brodie, A. M. J. Med. Chem. 1998, 41, 902-912.
http://dx.doi.org/10.1021/jm970568r

[28]. Brodie, A.; Njar, V. C. US Patent 6, 200, 965 B1; 2001.

[29]. Handratta, V. D.; Jelovac, D.; Long, B. J.; Kataria, R.; Nnane, I. P.; Njar, V. C.; Brodie, A. M. J. Steroid Biochem. Mol. Biol. 2004, 92, 155-165.

[30]. Handratta, V. D.; Vasaitis, T. S.; Njar, V. C.; Gediya, L. K.; Kataria, R.; Chopra, P.; Newman, P.; Farquhar, R.; Guo, Z.; Qiu, Y.; Brodie, A. M. J. Med. Chem. 2005, 48, 2972-2984.
http://dx.doi.org/10.1021/jm040202w

[31]. Brodie, A.; Njar, V. C. WO Patent 2006/093993, 2006.

[32]. Vasaitis, T. S.; Njar, V. C. O. Future Med. Chem. 2010, 2, 667-680.
http://dx.doi.org/10.4155/fmc.10.14

[33]. Molina, A.; Belldegrun, A. J. Urol. 2011, 185, 787-794.
http://dx.doi.org/10.1016/j.juro.2010.10.042

[34]. de Bono, J. S.; Logothetis, C. J.; Molina, A.; Fizazi, K.; North, S.; Chu, L.; Chi, K. N.; Jones, R. J.; et al. N. Engl. J. Med. 2011, 364, 1995-2005.
http://dx.doi.org/10.1056/NEJMoa1014618

[35]. Bryce, A.; Ryan, C. J. Clin. Pharma. Therap. 2012, 91, 101-108.
http://dx.doi.org/10.1038/clpt.2011.275

[36]. Potter, G. A.; Barrie, S. E.; Jarman, M.; Rowlands, M. G. J. Med. Chem. 1995, 38, 2463-2471.
http://dx.doi.org/10.1021/jm00013a022

[37]. Al-Masoudi, N. A.; Ali, D. S.; Saeed, B.; Hartmann, R. W.; Engel, M.; Rashid, S.; Saeed, A. Archiv Pharmazie Life Sci. 2014, 347, 896-907.

[38]. Mitsunobu, O.; Yamada, M. Bull. Chem. Soc. Jpn. 1967, 40, 2380-2382.
http://dx.doi.org/10.1246/bcsj.40.2380

[39]. Mitsunobu, O. Synthesis 1981, 1, 1-28.
http://dx.doi.org/10.1055/s-1981-29317

[40]. Mitsunobu, O.; Eguchi, M. Bull. Chem. Soc. Jpn. 1971, 44, 3427-3430.
http://dx.doi.org/10.1246/bcsj.44.3427

[41]. Willker, W.; Leibfritz, D.; Kerssebaum, R.; Bermel, W. Mag. Reson. Chem. 1993, 31, 287-292
http://dx.doi.org/10.1002/mrc.1260310315

[42]. Davis, A. L.; Keeler, J.; Laue, E. D.; Moskau, D. J. Magn. Reson. 1992, 98, 207-216.

[43]. Anderson, W. A.; Freeman, R. J. Chem. Phys. 1962, 37, 411-415.

[44]. Pauwels, R.; Balzarini, J.; Baba, M.; Snoeck, R.; Schols, D.; Herdewijn, P.; Desmyter, J.; De Clercq, E. J. Virol. Methods 1988, 20, 309-321.
http://dx.doi.org/10.1016/0166-0934(88)90134-6

[45]. Hargrave, K. D.; Proudfoot, J. R.; Grozinger, K. G.; Cullen, E.; Kapadia, S. R.; Patel, U. R.; Fuchs, V. U.; Mauldin, S. C.; Vitous, J.; Behnke, M. L.; Klunder, J. M.; Pal, K.; Skiles, J. W.; McNeil, D. W.; Rose, J. M.; Chow, G. C.; Skoog, M. T.; Wu, J. C.; Schmidt, G.; Engel, W. W.; Eberlein, W. G.; Saboe, T. D.; Campbell, S. J.; Rosenthal, A. S.; Adams, J. J. Med. Chem. 1991, 34, 2231-2241.
http://dx.doi.org/10.1021/jm00111a045

[46]. Mitsuya, H.; Weinhold, K. J.; Furman, P. A.; Clair, M. H. St.; Lehrmann, S. N.; Gallo, R.; Bolognesi, D.; Barry, D. W.; Broder, S. Proc. Natl. Acad. Sci. USA 1985, 82, 7096-7100.
http://dx.doi.org/10.1073/pnas.82.20.7096

[47]. Seeliger, S.; de Groot, B. L. J. Computer-Aided Mol. Design 2010, 24, 417-422.

[48]. Zhan, P.; Liu, X.; Li, Z.; Fang, Z.; Pannecouque, C.; De Clercq, E. Chem. Biodivers. 2010, 7, 1717-1727.
http://dx.doi.org/10.1002/cbdv.200900197

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