Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates

被引：4

作者：

El-Naggar, Mohamed ^{[1
]}

Amr, Abd El-Galil E. ^{[2
,3
]}

Fayed, Ahmed A. ^{[3
,4
]}

Elsayed, Elsayed A. ^{[5
,6
]}

Al-Omar, Mohamed A. ^{[2
]}

Abdalla, Mohamed M. ^{[7
]}

机构：

[1] Univ Sharjah, Fac Sci, Chem Dept, Sharjah 27272, U Arab Emirates

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

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

[4] Taibah Univ, Coll Med Rehabil Sci, Resp Therapy Dept, Madinah Munawara 22624, Saudi Arabia

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

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

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

来源：

MOLECULES | 2019年 / 24卷 / 11期

关键词：

estrone derivatives; hydrazine; N-substituted pyrazoline; anti-ovarian cancer; topoisomerase II inhibitor; kinase inhibitor; IN-VITRO; PROLIFERATION; CYTOTOXICITY; DERIVATIVES; PATHWAYS; ALPHA; VIVO;

D O I：

10.3390/molecules24112054

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 16-(-alkoxyalkane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol (3a-l) and estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol derivatives (4a-d) were synthesized from corresponding arylidines 2a,b which was prepared from estrone 1 as starting material. Condensation of 1 with aldehydes gave the corresponding arylidine derivatives 2a,b which were treated with hydrazine derivatives in alcohols to give the corresponding derivatives 3a-l, respectively. Additionally, treatment of 2a,b with methyl- or phenylhydrazine in ethanolic potassium hydroxide afforded the corresponding N-substituted pyrazoline derivatives 4a-d, respectively. All these derivatives showed potent anti-ovarian cancer both in vitro and in vivo. The mechanism of anti-ovarian cancer was suggested to process via topoisomerase II and (V600E)BRAF inhibition.

引用

页数：15

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