Tumor microenvironment is a complex multistep event which involves several hallmarks that transform the normal cell into cancerous cell. Designing the novel antagonistic molecule to reverse the tumor microenvironment with specific target is essential in modern biological studies. The novel 4-phenyl-2-phenoxyacetamide thiazole analogues 8_a-ab were synthesized in multistep process, then screened and assessed for cytotoxic and anti-proliferative effects in vitro against multiple cancer cells of different origin such as MCF-7, A549, EAC and DLA cells which revealed that compound 8f with fluoro and methyl substitute has potential cytotoxic efficacy with an average IC₅₀ value of ˜ 13 μM. The mechanism of cytotoxicity assessed for anti-tumor studies both in ascites and solid tumor models in-vivo inferred the regressed tumor activity. This is due to changes in the cause of tumor microenvironment with crackdown of neovascularization and evoking apoptosis process as assessed by CAM, corneal vascularization and apoptotic hallmarks in 8f treated cells. The molecular gene studies inferred involvement of HIF-1upregulation and stabilization of p53 which are interlinked in signaling as conferred by immunoblot analysis.

肿瘤微环境是一个复杂的多步骤事件，涉及多个将正常细胞转化为癌细胞的标志。设计新颖的拮抗分子以特定的靶点逆转肿瘤微环境在现代生物学研究中至关重要。多步合成了新颖的4-苯基-2-苯氧基乙酰胺噻唑类似物8 _a-ab，然后筛选并评估了其对多种来源的多种癌细胞（如MCF-7，A549，EAC）的体外细胞毒性和抗增殖作用和DLA细胞，揭示具有氟和甲基取代基的化合物8f具有潜在的细胞毒性功效，平均IC ₅₀〜13μM的值。在体内腹水和实体瘤模型中针对抗肿瘤研究评估的细胞毒性机制均能推断出肿瘤的消退活性。这是由于通过8f处理的细胞中的CAM，角膜血管化和凋亡标志所评估的肿瘤微环境病因的改变，包括新血管形成的抑制和诱发凋亡过程。分子基因研究推断HIF-1的上调和p53的稳定作用与免疫印迹分析所赋予的信号传导是相互联系的。