Design, Synthesis, Anticancer Evaluation and Molecular Modeling of Novel Estrogen Derivatives

被引：32

作者：

Amr, Abd El-Galil E. ^{[1
,2
]}

Elsayed, Elsayed A. ^{[3
,4
]}

Al-Omar, Mohamed A. ^{[1
]}

Eldin, Hanan O. Badr ^{[5
,6
]}

Nossier, Eman S. ^{[7
]}

Abdallah, Mohamed M. ^{[8
]}

机构：

[1] King Saud Univ, Coll Pharm, Pharmaceut Chem Dept, DEDC, Riyadh 11451, Saudi Arabia

[2] Natl Res Ctr, Appl Organ Chem Dept, Cairo 12622, Dokki, Egypt

[3] King Saud Univ, Fac Sci, Bioprod Res Chair, Zool Dept, Riyadh 11451, Saudi Arabia

[4] Natl Res Ctr, Chem Nat & Microbial Prod Dept, Cairo 12622, Dokki, Egypt

[5] King Khalid Univ, Fac Sci, Chem Dept, Mahailasir 61421, Saudi Arabia

[6] Natl Res Ctr, Text Ind Div, Dept Dyeing, Cairo 12622, Dokki, Egypt

[7] Al Azhar Univ, Fac Pharm Girls, Pharmaceut Med Chem Dept, Cairo 11754, Egypt

[8] Atos Pharma, Belbis 44621, El Sharkya, Egypt

来源：

MOLECULES | 2019年 / 24卷 / 03期

关键词：

estrogen derivatives; design; anticancer evaluation; molecular modeling studies; IN-VIVO; PROSTATE-CANCER; BREAST-CANCER; SCHIFF-BASES; VITRO; INHIBITION; STEROIDS; RING; P53; MDM2;

D O I：

10.3390/molecules24030416

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 series of estrone derivatives 3-8 was designed and synthesized using estrone arylmethylenes 2a,b as starting materials and their structures were confirmed by different spectral data and elemental analyses. All the newly synthesized compounds exhibited potent in vitro and in vivo cytotoxic activities against breast cancer cell lines. In addition, all compounds were subjected to in vitro and in vivo inhibition assays for EGFR and VEGFR-2 kinases as well as p53 ubiquitination activity to obtain more details about their mechanism of action. Based on the promising results, a molecular docking study was investigated for the most representative compound 5a against the two targets, EGFR and VEGFR-2 kinases, to assess its binding affinity, hoping to rationalize and obtain potent anticancer agents in the future.

引用

页数：18

共 44 条

[1] Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors for chemoprevention of cancer [J].

Abdalla, Mohamed M. ;

Al-Omar, Mohamed A. ;

Bhat, Mashooq A. ;

Amr, Abdel-Galil E. ;

Al-Mohizea, Abdullah M. .

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2012, 50 (04) :1127-1132

[2] Synthesis and reactions of thiosemicarbazides, triazoles, and Schiff bases as antihypertensive α-blocking agents [J].

Abdel-Wahab, Bakr F. ;

Mohamed, Salwa F. ;

Amr, Abd El-Galil E. ;

Abdalla, Mohamed M. .

MONATSHEFTE FUR CHEMIE, 2008, 139 (09) :1083-1090

[3] Synthesis of Some New Pyridine-2,6-carboxamide-derived Schiff Bases as Potential Antimicrobial Agents [J].

Al-Omar, Mohamed A. ;

Amr, Abd El-Galil E. .

MOLECULES, 2010, 15 (07) :4711-4721

[4] Synthesis of new (Nα-dipicolinoyl)-bis-L-valyl-L-phenylalanyl linear and macrocyclic bridged peptides as anti-inflammatory agents [J].

Amr, Abd El-Galil E. ;

Abo-Ghalia, Mohamed H. ;

Abdalah, Mohamed M. .

ARCHIV DER PHARMAZIE, 2007, 340 (06) :304-309

[5] Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as Anticancer Multi-Targeted Kinase Inhibitors [J].

Amr, Abd El-Galil E. ;

Abo-Ghalia, Mohamed H. ;

Moustafa, Gaber O. ;

Al-Omar, Mohamed A. ;

Nossier, Eman S. ;

Elsayed, Elsayed A. .

MOLECULES, 2018, 23 (10)

[6] In Vitro and In Vivo Anti-Breast Cancer Activities of Some Synthesized Pyrazolinyl-estran-17-one Candidates [J].

Amr, Abd El-Galil E. ;

El-Naggar, Mohamed ;

Al-Omar, Mohamed A. ;

Elsayed, Elsayed Ahmed ;

Abdalla, Mohamed M. .

MOLECULES, 2018, 23 (07)

[7]

Amr Abd El-Galil El-Sayed, 2006, Acta Pharmaceutica (Zagreb), V56, P203

[8] Synthesis and anti-inflammatory activities of new cyanopyrane derivatives fused with steroidal nuclei [J].

Amr, AGE ;

Abdulla, MM .

ARCHIV DER PHARMAZIE, 2006, 339 (02) :88-95

[9] Impact of estradiol structural modifications (18-methyl and/or 17-hydroxy inversion of configuration) on the in vitro and in vivo estrogenic activity [J].

Ayan, Diana ;

Roy, Jenny ;

Maltais, Rene ;

Poirier, Donald .

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2011, 127 (3-5) :324-330

[10]

Breitmaier Eberhard., 1993, STRUCTURE ELUCIDATIO, P27

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