European Journal of Chemistry 2015, 6(1), 1-7. doi:10.5155/eurjchem.6.1.1-7.1139

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

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

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DOI: 10.5155/eurjchem.6.1.1-7.1139

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Citations

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[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
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[2]. 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
/


[3]. 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
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[4]. 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
/


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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. 16 Sep. 2019
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

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