Synthesis of Novel 2-((3-(Benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl-4-phenylthiazole: Potent EGFR Targeting Anticancer Agents

被引:5
作者
Amudala, Sateesh [1 ]
Palabindela, Rambabu [2 ,3 ]
Bhoomandla, Srinu [4 ]
Kotilingaiah, N. [5 ]
Sandhya, Jonnala [6 ]
Mandala, Jyothi [1 ]
机构
[1] Mahatma Gandhi Univ, Dept Chem & Pharmaceut Sci, Nalgonda 508254, Telangana, India
[2] Guru Nanak Inst, Dept Chem, Tech Campus, Hyderabad 501506, Ibrahimpatnam, India
[3] Kakatiya Univ, Dept Chem, Warangal 506009, Telangana, India
[4] Geethanjali Coll Engn & Technol, Dept Chem, Cheeryal 501301, Telangana, India
[5] Guru Nanak Inst Technol, Dept Chem, Hyderabad 501506, Andhra Pradesh, India
[6] Vaageswari Coll Engn, Dept Chem, Karimnagar 505481, Telangana, India
关键词
benzofuran-pyrazole containing amino thiazoles; anticancer activity; EGFR; docking; THIAZOLE HYBRIDS;
D O I
10.1134/S1068162024010138
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
Objective: Benzofurans, fused pyrazole systems, and thiazole moieties are the most important pharmacophores and intermediates for making drugs. The preparation and anti-cancer activity of novel benzofuran-pyrazole-containing amino thiazole hybrids. Methods: The synthesized benzofuran-pyrazole containing amino thiazole hybrids (VIIa-VIIi). The anticancer activity of (VIIa-VIIi) against MCF-7, and A549 cell lines was determined using the MTT-assay, and also screened with in silico molecular docking studies. Results: The most potent compounds (E)-2-(2-((3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-4-(4-chlorophenyl)thiazole (VIIg) and (E)-2-(2-((3-(benzofuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinyl)-4-(p-tolyl)thiazole (VIIb) exhibited excellent anticancer activity against the MCF-7 and A549 cancer cell lines. Additionally, the synthesis hybrids and Erlotinib were screened for their in silico molecular docking studies against the EGFR (4HJO) receptor. The compounds (VIIg) and (VIIb) exhibited significantly higher binding scores and inhibitory constants than the reference drug Erlotinib. Conclusions: It has been observed that the substitution on the 4-chloro phenyl ring (VIIg) and 4-methyl phenyl ring (VIIb) important for maintaining their anticancer activity. The outcomes of the kinase inhibitory assay of these significant (VIIg) and (VIIb) hybrids against the tyrosine kinase EGFR strongly corroborated the in vitro anticancer findings and the in silico docking investigations. This research showed that newly developed compounds have potential as anticancer agents and suggested leads for further research.
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收藏
页码:34 / 44
页数:11
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