VEGFR-2 İnhibisyonu Üzerinden Antiproliferatif Etki Potansiyeline Sahip Yeni Pirazol Türevlerinin Tasarımı, Sentezi ve Farmakolojik Aktivitelerinin Araştırılması
Abstract
Kanser, moleküler düzeyde çoklu sinyal yolaklarının düzensizleşmesiyle karakterize edilen, kompleks ve heterojen bir hastalık grubudur. Anjiyogenez süreci, solid tümörlerin büyümesi ve metastazı için kritik öneme sahiptir. Bu süreçte anahtar bir rol oynayan VEGFR-2 reseptörü, son yıllarda hedefe yönelik tedavi yaklaşımlarının odak noktası hâline gelmiştir. Bu çalışmada, VEGFR-2 inhibitörü potansiyeline sahip yeni pirazol ve benzoksazol türevleri farmakofor yaklaşımlar doğrultusunda tasarlanmış, klasik organik sentez yöntemleri ile sentezlenmiş ve karakterizasyonları gerçekleştirilmiştir. Tasarlanan moleküller, literatürdeki seçici VEGFR-2 inhibitörleriyle karşılaştırmalı olarak değerlendirilmiş, yapı–etki ilişkileri irdelenmiş ve farmakolojik potansiyelleri teorik olarak yorumlanmıştır. Ayrıca bileşiklerin VEGFR-2 hedefine karşı bağlanma afinitesi moleküler docking yöntemleri ile irdelenmiştir. Çalışma, yeni bileşiklerin geliştirilmesinde yapısal çeşitliliğin önemini vurgulamakta ve VEGFR-2'yi hedef alan ilaç tasarımı sürecine katkı sağlayacak nitelikte bir güncel literatür zemini sunmaktadır. Anahtar Kelimeler: Anjiyogenez, Benzoksazol, Pirazol,
Cancer is a complex and heterogeneous group of diseases characterized by dysregulation in multiple molecular signaling pathways. Angiogenesis plays a crucial role in tumor growth and metastasis, and VEGFR-2 is one of the key receptors regulating this process. In this study, novel pyrazole and benzoxazole derivatives with potential VEGFR-2 inhibitory activity were designed using pharmacophore-based strategies, synthesized via conventional organic methods, and structurally characterized. The synthesized compounds were evaluated in comparison with known VEGFR-2 inhibitors reported in the literature, and their structure–activity relationships were analyzed. Additionally, the binding affinity of the compounds toward the VEGFR-2 target was investigated using molecular docking methods. This work emphasizes the importance of structural diversity in rational drug design and provides a current scientific framework for future studies targeting VEGFR-2.
Cancer is a complex and heterogeneous group of diseases characterized by dysregulation in multiple molecular signaling pathways. Angiogenesis plays a crucial role in tumor growth and metastasis, and VEGFR-2 is one of the key receptors regulating this process. In this study, novel pyrazole and benzoxazole derivatives with potential VEGFR-2 inhibitory activity were designed using pharmacophore-based strategies, synthesized via conventional organic methods, and structurally characterized. The synthesized compounds were evaluated in comparison with known VEGFR-2 inhibitors reported in the literature, and their structure–activity relationships were analyzed. Additionally, the binding affinity of the compounds toward the VEGFR-2 target was investigated using molecular docking methods. This work emphasizes the importance of structural diversity in rational drug design and provides a current scientific framework for future studies targeting VEGFR-2.
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Keywords
Eczacılık ve Farmakoloji, Anjiyogenez İnhibitörleri, Benzoksazoller, Pirazol, Pharmacy and Pharmacology, Angiogenesis Inhibitors, Benzoxazoles, Pyrazole
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