European Journal of Chemistry 2015, 6(1), 1-7 | doi: https://doi.org/10.5155/eurjchem.6.1.1-7.1139 | Get rights and content






  OPEN ACCESS | PEER-REVIEWED | RESEARCH ARTICLE | DOWNLOAD PDF | VIEW FULL-TEXT PDF | TOTAL VIEWS

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


Kuthair Mohammed Mahdi (1) , Nabeel Abed Abdul-Reda (2) , Najim Aboud Al-Masoudi (3,*)

(1) Department of Chemistry, College of Education, University of Qadisiya, Qadisiya, 58002, Iraq
(2) Department of Chemistry, College of Education, University of Qadisiya, Qadisiya, 58002, Iraq
(3) Department of Chemistry, College of Science, University of Basrah, Basrah, 61004, Iraq
(*) Corresponding Author

Received: 31 Aug 2014 | Accepted: 29 Oct 2014 | Published: 31 Mar 2015 | Issue Date: March 2015

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.


Keywords


Steriods; Pregnenolone; Anti-HIV activity; Mitsunobu reaction; Molecular modeling study; 17α-Hydroxylase/C17,20-lyase

Full Text:

PDF /    /


DOI: 10.5155/eurjchem.6.1.1-7.1139

Links for Article


| | | | |

| | | | | | |

Related Articles




Article Metrics

This Abstract was viewed 755 times | PDF Article downloaded 262 times


Citations

/


[1]. Sharad Kumar Panday
Advances in the Mitsunobu Reaction: An Excellent Organic Protocol with Versatile Applications
Mini-Reviews in Organic Chemistry  16(2), 127, 2019
DOI: 10.2174/1570193X15666180612090313
/


[2]. Nabeel Abed Abdul-Reda, Aqeel Abed Muhee
Synthesis, Characterization and biological Study of some new derivatives from Pregnenolone via McMurry reaction
Journal of Physics: Conference Series  1294, 052023, 2019
DOI: 10.1088/1742-6596/1294/5/052023
/


[3]. Najim A. Al-Masoudi, Nabeel A. Abdul-Rida, Rawaa A. Kadhim, Sebastian J. Krug, Matthias Engel, Bahjat A. Saeed
Synthesis and CYP17α hydroxylase inhibition activity of new 3α- and 3β-ester derivatives of pregnenolone and related ether analogues
Medicinal Chemistry Research  25(2), 310, 2016
DOI: 10.1007/s00044-015-1480-z
/


[4]. Mohammed Abed Al-Hussein Salman, Nabeel Abed Abdul-Rida
Synthesis of new derivatives of aryl-clonazepam via Suzuki Cross-coupling reaction
European Journal of Chemistry  7(2), 152, 2016
DOI: 10.5155/eurjchem.7.2.152-155.1403
/


[5]. Najim A. Al-Masoudi, Kuthiar M. Mahdi, Nabeel A. Abdul-Rida, Bahjat A. Saeed, Mathias Engel
A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study
Steroids  100, 52, 2015
DOI: 10.1016/j.steroids.2015.05.002
/


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

How to cite


Mahdi, K.; Abdul-Reda, N.; Al-Masoudi, N. Eur. J. Chem. 2015, 6(1), 1-7. doi:10.5155/eurjchem.6.1.1-7.1139
Mahdi, K.; Abdul-Reda, N.; Al-Masoudi, N. Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study. Eur. J. Chem. 2015, 6(1), 1-7. doi:10.5155/eurjchem.6.1.1-7.1139
Mahdi, K., Abdul-Reda, N., & Al-Masoudi, N. (2015). Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study. European Journal of Chemistry, 6(1), 1-7. doi:10.5155/eurjchem.6.1.1-7.1139
Mahdi, Kuthair, Nabeel Abed Abdul-Reda, & Najim Aboud Al-Masoudi. "Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study." European Journal of Chemistry [Online], 6.1 (2015): 1-7. Web. 17 Jan. 2020
Mahdi, Kuthair, Abdul-Reda, Nabeel, AND Al-Masoudi, Najim. "Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study" European Journal of Chemistry [Online], Volume 6 Number 1 (31 March 2015)

DOI Link: https://doi.org/10.5155/eurjchem.6.1.1-7.1139

| | | | |

| | | | | |

Save to Zotero Save to Mendeley

European Journal of Chemistry 2015, 6(1), 1-7 | doi: https://doi.org/10.5155/eurjchem.6.1.1-7.1139 | Get rights and content

Refbacks

  • There are currently no refbacks.




Copyright (c)




© Copyright 2019  Atlanta Publishing House LLC All Right Reserved.

The opinions expressed in all articles published in European Journal of Chemistry are those of the specific author(s), and do not necessarily reflect the views of Atlanta Publishing House LLC, or European Journal of Chemistry, or any of its employees.

Copyright 2019 Atlanta Publishing House LLC. All rights reserved. This site is owned and operated by Atlanta Publishing House LLC whose registered office is 4614 Lavista road, Tucker, GA, 30084, USA. Registered in USA.