European Journal of Chemistry

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

Main Article Content

Kuthair Mohammed Mahdi
Nabeel Abed Abdul-Reda
Najim Aboud Al-Masoudi


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.

icon graph This Abstract was viewed 1736 times | icon graph Article PDF downloaded 736 times

How to Cite
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.

Article Details

Crossref - Scopus - Google - European PMC

[1]. Mensah-Nyagan, A. G.; Meyer, L.; Schaeffer, V.; Kibaly, C.; Patte-Mensah, C. Psychoneuroendocrino. 2009, 34, 169-177.

[2]. Ibrahim-Ouali, M. Steroids 2007, 72, 475-508.

[3]. Bhatti, H. N.; Khera, R. A. Steroids 2012, 77, 1267-1290.

[4]. Aggarwal, S.; Thareja, S.; Verma, A.; Bhardwaj, T. R.; Kumar, M. Steroids 2010, 75, 109-153.

[5]. Li, H. J.; Jiang, Y.; Li, P. Nat. Prod. Rep. 2006, 23, 735-752.

[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.

[7]. Bansal, R.; Guleria, S.; Thota, S.; Bodhankar, S. L.; Patwardhan, M. R.; Zimmer, C. Steroids 2012, 77, 621-629.

[8]. Dubey, R. K.; Oparil, S.; Imthurn, B.; Jackson, E. K. Cardiovasc. Res. 2002, 53, 688-708.

[9]. Holst, J. P.; Soldin, S. J.; Tractenberg, R. E.; Guo, T.; Kundra, P.; Verbalis, J. G. Steroids 2007, 72, 71-84.

[10]. Auci, D. L.; Reading, C. L.; Frincke, J. M. Autoimmun Rev. 2009, 8, 369-372.

[11]. Jursic, B. S.; Upadhyay, S. K.; Creech, C. C.; Neumann, D. M. Bioorg. Med. Chem. Lett. 2010, 20, 7372-7375.

[12]. Banday, A. H.; Iqbal, Z. M.; Ganaie, B. A. Steroids 2011, 76, 1358-1362.

[13]. Billich, A.; Nussbaumer, P.; Lehr, P. J. Steroid Biochem. 2000, 73, 225-235.

[14]. Saha, P.; Fortin, S.; Leblanc, V.; Parent, S.; Asselin, E.; Berube, G. Steroids 2012, 77, 1113-1122.

[15]. Bansal, R.; Guleria, S.; Thota, S.; Hartmann, R. W.; Zimmer, C. Chem. Pharma. Bull. 2011, 59, 327-331.

[16]. Gauthier, S.; Martel, C.; Labrie, F. J. Steroid Biochem. 2012, 132, 93-104.

[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.

[19]. Aird, R. B. J. Nerv. Mental Dis. 1944, 99, 501-510.

[20]. Aird, R. B.; Gordan, G. S. J. Am. Med. Assoc. 1951, 145, 715-719.

[21]. Gyermek, L.; Genther, G.; Fleming, N. Intern. J. Neuropharm. 1967, 6, 191-198.

[22]. Green, C. J.; Halsey, M. J.; Precious, S.; Wardley-Smith, B. Lab. Animals 1978, 12, 85-89.

[23]. Moffat, L. E.; Kirk, D.; Tolley, D. A.; Smith, M. F.; Beastall, G. British J. Urology 1988, 61, 439-440.

[24]. Mahler, C.; Verhelst, J.; Denis, L. Cancer 1993, 71, 1068-1073.<1068::AID-CNCR2820711427>3.0.CO;2-5

[25]. Lake-Bakaar, G.; Scheuer, P. J.; Sherlock, S. British Med. J. 1987, 294, 419-442.

[26]. Njar, V. C.; . Klus, G. T.; Brodie, A. M. H. Bioorg. Med. Chem. Lett. 1996, 6, 2777-2782.

[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.

[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.

[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.

[33]. Molina, A.; Belldegrun, A. J. Urol. 2011, 185, 787-794.

[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.

[35]. Bryce, A.; Ryan, C. J. Clin. Pharma. Therap. 2012, 91, 101-108.

[36]. Potter, G. A.; Barrie, S. E.; Jarman, M.; Rowlands, M. G. J. Med. Chem. 1995, 38, 2463-2471.

[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.

[39]. Mitsunobu, O. Synthesis 1981, 1, 1-28.

[40]. Mitsunobu, O.; Eguchi, M. Bull. Chem. Soc. Jpn. 1971, 44, 3427-3430.

[41]. Willker, W.; Leibfritz, D.; Kerssebaum, R.; Bermel, W. Mag. Reson. Chem. 1993, 31, 287-292

[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.

[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.

[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.

[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.

Most read articles by the same author(s)

Dimensions - Altmetric - scite_ - PlumX

Downloads and views


Download data is not yet available.


Metrics Loading ...
License Terms

License Terms


Copyright © 2024 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License ( By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License ( are administered by Atlanta Publishing House LLC (European Journal of Chemistry).