Design, Synthesis and Cytotoxicity Screening of New Thiazole Derivatives as Potential Anticancer Agents through VEGFR-2 Inhibition

被引：15

作者：

Al-Warhi, Tarfah ^{[1
]}

Abualnaja, Matokah ^{[2
]}

Abu Ali, Ola A. ^{[3
]}

Alyamani, Najiah M. ^{[4
]}

Elsaid, Fahmy G. ^{[5
,6
]}

Shati, Ali A. ^{[5
]}

Albogami, Sarah ^{[7
]}

Fayad, Eman ^{[7
]}

Abu Almaaty, Ali H. ^{[8
]}

Mohamed, Khaled O. ^{[9
]}

Alamoudi, Wael M. ^{[10
]}

Zaki, Islam ^{[11
]}

机构：

[1] Princess Nourah Bint Abdulrahman Univ, Coll Sci, Dept Chem, POB 84428, Riyadh 11671, Saudi Arabia

[2] Umm Al Qura Univ, Fac Appl Sci, Dept Chem, Makkah Al Mukarrama 24381, Saudi Arabia

[3] Taif Univ, Coll Sci, Dept Chem, POB 11099, Taif 21944, Saudi Arabia

[4] Univ Jeddah, Coll Sci, Biol Dept, Jeddah 23218, Saudi Arabia

[5] King Khalid Univ, Coll Sci, Biol Dept, Abha 61421, Saudi Arabia

[6] Mansoura Univ, Fac Sci, Zool Dept, Mansoura 35516, Egypt

[7] Taif Univ, Fac Sci, Dept Biotechnol, POB 11099, Taif 21944, Saudi Arabia

[8] Port Said Univ, Fac Sci, Zool Dept, Port Said 42526, Egypt

[9] Cairo Univ, Fac Pharm, Pharmaceut Organ Chem Dept, Cairo 11562, Egypt

[10] Umm Al Qura Univ, Fac Appl Sci, Dept Biol, Makkah Al Mukarrama 24382, Saudi Arabia

[11] Port Said Univ, Fac Pharm, Pharmaceut Organ Chem Dept, Port Said 42526, Egypt

来源：

SYMMETRY-BASEL | 2022年 / 14卷 / 09期

关键词：

Z-configurated isomers; thiazole; hydrazinecarbothioamide; phenacylbromide; cytotoxicity; VEGFR-2; apoptosis; p53; mitochondrial membrane potential (MMP);

D O I：

10.3390/sym14091814

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Z-configurated isomers are kinetically preferred molecules. Compounds with Z-configuration are contained in many natural products, biologically active compounds and as synthons for organic synthesis. Two series of new thiazole-based analogs were synthesized from appropriate starting materials hydrazinecarbothioamide derivatives (Z)-2a,b to be evaluated for their inhibitory activity towards VEGFR-2. The prepared thiazole compounds 3a-5b were screened for their cytotoxic potency against the MDA-MB-231 breast cancer cell line and their percentage inhibition against VEGFR-2. Compound 4d exhibited good VEGFR-2 inhibitory activity. A DNA flow cytometry analysis was conducted, and compound 4d demonstrated cell cycle arrest at the G1 and G2/M phases of the cell cycle profile and an apoptosis-inducing effect by increasing the percentage of pre-G1 phase. Compound 4d was further evaluated for its apoptosis-inducing effect by studying the effect on mitochondrial membrane potential (MMP) and p53 activation. It was found to boost the level of p53 and reduce the level of MMP compared with the untreated control cells.

引用

页数：16

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