Synthesis of Imidazole-2,3-dihydrothiazole Compounds as VEGFR-2 Inhibitors and Their Support with in Silico Studies

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Atıf İçin Kopyala

OSMANİYE D., Bozkurt N. B., Kurban B., Yardimci G. B., ÖZKAY Y., KAPLANCIKLI Z. A.

CHEMISTRY & BIODIVERSITY, cilt.20, sa.9, 2023 (SCI-Expanded)

• Yayın Türü: Makale / Tam Makale
• Cilt numarası: 20 Sayı: 9
• Basım Tarihi: 2023
• Doi Numarası: 10.1002/cbdv.202300944
• Dergi Adı: CHEMISTRY & BIODIVERSITY
• Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
• Anahtar Kelimeler: 2,3-dihydrothiazole, imidazole, molecular docking, molecular dynamics, VEGFR-2
• Anadolu Üniversitesi Adresli: Evet

Özet

In this study, 12 novel 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-3-ethyl-4-(substitutephenyl)-2,3-dihydrothiazole derivatives were obtained. Among these compounds, 2-((1-(4-(1H-imidazol-1-yl)phenyl)ethylidene)hydrazineylidene)-4-([1,1 & PRIME;-biphenyl]-4-yl)-3-ethyl-2,3-dihydrothiazole (4h) was chosen as the most active derivative in the series. According to the MTT results, compounds 4h and 4k showed activity with IC50=4.566 & PLUSMN;0.246 & mu;M and IC50=4.537 & PLUSMN;0.463 & mu;M, respectively. Unlike other derivatives, compound 4h carries a phenyl ring in the 4th position of the phenyl ring. This bulky group allowed the compound to settle in the enzyme active site. Dynamic studies show that the stability of the compound does not change over 40 ns. RMSD, RMSF and Rg parameters all remained within acceptable limits. The uninterrupted aromatic hydrogen bonding of the enzyme active site with the important amino acids Cys919, Glu885 and Asp1046 proves the inhibitory potential of compound 4h on the VEGFR-2 enzyme. It is thought that more active compounds will be reached with the derivatives to be synthesized starting from compound 4h.