A new pregnenolone analogues as privileged scaffolds in inhibition of CYP17 hydroxylase enzyme. Synthesis and in silico molecular docking study

被引：5
|
作者：
Al-Masoudi, Najim A. [1 ]
Mahdi, Kuthiar M. [2 ]
Abdul-Rida, Nabeel A. [2 ]
Saeed, Bahjat A. [3 ]
Engel, Mathias [4 ]
机构：
[1] Univ Basrah, Coll Sci, Dept Chem, Basrah, Iraq
[2] Univ Qadisiya, Coll Educ, Dept Chem, Qadisiya, Iraq
[3] Univ Basrah, Coll Educ, Dept Chem, Basrah, Iraq
[4] Univ Saarland, Inst Pharmazeut & Med Chem, D-81310 Saarbrucken, Germany
来源：
STEROIDS | 2015年 / 100卷
关键词：
CYP17; hydroxylase; Imine analogues; Molecular docking; Pregnenolone; Prostate cancer; PROSTATE-CANCER; BIOLOGICAL EVALUATION; ABIRATERONE ACETATE; ANTITUMOR-ACTIVITY; CYP-17; INHIBITORS; AGENTS; PHARMACOKINETICS; P450(17-ALPHA); SUBSTITUTION; DERIVATIVES;
D O I：
10.1016/j.steroids.2015.05.002
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A new series of 17-(N-(arylimino)-5-pregnen-3 beta-ol derivatives 19-32 as well as carboxylate and acrylate analogues of pregnenolone 37-40 were synthesized and evaluated for their inhibitory activity against human CYP17 hydroxylase expressed in Escherichia coli. Compounds 32 and 37 were the Most potent analogues in this series, showing inhibition activity with IC50 = 2.11 and 1.29 mu M, respectively. However, the analogue 37 revealed a better selectivity profile (83.21% inhibition of hydroxylase), which is a leading candidate for further development. Molecular docking study of 37 showed binding with the amino acid residues of CYP17 through hydrogen bonds and hydrophobic interaction. (C) 2015 Published by Elsevier Inc.
引用
收藏
页码：52 / 59
页数：8
相关论文
共 50 条
  • [1] New CYP17 Hydroxylase Inhibitors: Synthesis, Biological Evaluation, QSAR, and Molecular Docking Study of New Pregnenolone Analogs
    Al-Masoudi, Najim A.
    Ali, Dawood S.
    Saeed, Bahjat
    Hartmann, Rolf W.
    Engel, Matthias
    Rashid, Sajid
    Saeed, Aamer
    ARCHIV DER PHARMAZIE, 2014, 347 (12) : 896 - 907
  • [2] Synthesis and CYP17α hydroxylase inhibition activity of new 3α- and 3β-ester derivatives of pregnenolone and related ether analogues
    Najim A. Al-Masoudi
    Nabeel A. Abdul-Rida
    Rawaa A. Kadhim
    Sebastian J. Krug
    Matthias Engel
    Bahjat A. Saeed
    Medicinal Chemistry Research, 2016, 25 : 310 - 321
  • [3] Synthesis and CYP17α hydroxylase inhibition activity of new 3α- and 3β-ester derivatives of pregnenolone and related ether analogues
    Al-Masoudi, Najim A.
    Abdul-Rida, Nabeel A.
    Kadhim, Rawaa A.
    Krug, Sebastian J.
    Engel, Matthias
    Saeed, Bahjat A.
    MEDICINAL CHEMISTRY RESEARCH, 2016, 25 (02) : 310 - 321
  • [4] New biaryl-chalcone derivatives of pregnenolone via Suzuki-Miyaura cross-coupling reaction. Synthesis, CYP17 hydroxylase inhibition activity, QSAR, and molecular docking study
    Al-Masoudi, Najim A.
    Kadhim, Rawaa A.
    Abdul-Rida, Nabeel A.
    Saeed, Bahjat A.
    Engel, Matthias
    STEROIDS, 2015, 101 : 43 - 50
  • [5] Synthesis, in vitro α-glucosidase activity and in silico molecular docking study of isatin analogues
    Ullah, Hayat
    Rahim, Fazal
    Ullah, Ezaz
    Hayat, Shawkat
    Zada, Hussan
    Khan, Fahad
    Wadood, Abdul
    Nawaz, Faisal
    Rehman, Zia Ur
    Shah, Syed Adnan Ali
    CHEMICAL DATA COLLECTIONS, 2023, 43
  • [6] Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: Novel CYP17 inhibitors for the treatment of prostate cancer
    Mendieta, Mariano A. E. Pinto-Bazurco
    Negri, Matthias
    Jagusch, Carsten
    Vieira, Ursula Mueller
    Lauterbach, Thomas
    Hartmann, Rolf W.
    JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (16) : 5009 - 5018
  • [7] Androgen synthesis in a songbird:: A study of Cyp17 (17α-hydroxylase/C17,20-lyase) activity in the zebra finch
    Schlinger, BA
    Lane, NI
    Grisham, W
    Thompson, L
    GENERAL AND COMPARATIVE ENDOCRINOLOGY, 1999, 113 (01) : 46 - 58
  • [8] New thiosemicarbazones analogues-synthesis, urease inhibition, kinetics and molecular docking studies
    Rizvi, Fazila
    Khan, Majid
    Shah, Syed Zohaib Ahsan Mustafa
    Ali, Mohsin
    Siddiqui, Hina
    PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 2024, 199 (05) : 394 - 405
  • [9] Synthesis and Antimicrobial Activity of New Carbohydrazide Bearing Quinoline Scaffolds in Silico ADMET and Molecular Docking Studies
    Nipate, Amol S.
    Jadhav, Chetan K.
    Chate, Asha V.
    Dixit, Prashant P.
    Sharma, Prachi
    Gill, Charansingh H.
    POLYCYCLIC AROMATIC COMPOUNDS, 2024, 44 (02) : 1348 - 1365
  • [10] Design, synthesis, in vitro bio-evaluation and in silico molecular docking study of benzohydrazide based thiourea analogues
    Aleid, Ghadah
    Imran, Muhammad
    Ullah, Hayat
    Taha, Muhammad
    Khan, Javed
    Rahim, Fazal
    Hussain, Amjad
    Al-Shammari, Anoud
    Al-Marshedy, Sumayyah
    Ahmed, Wael
    Iqbal, Rashid
    Abdel-Hameed, Reda
    RESULTS IN CHEMISTRY, 2024, 11
12345