Synthesis and biological evaluation of salicylic acid conjugated isoxazoline analogues on immune cell proliferation and angiogenesis

• Published in: European journal of medicinal chemistry 2016-05, Vol.114, p.153-161
• Main Authors: Puttaswamy, Naveen, Pavan Kumar, G.S., Al-Ghorbani, Mohammed, Vigneshwaran, V., Prabhakar, B.T., Khanum, Shaukath Ara
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Angiogenesis Inducing Agents - chemical synthesis; Angiogenesis Inducing Agents - chemistry; Angiogenesis Inducing Agents - pharmacology; Animals; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells - drug effects; Endothelial Cells - immunology; HEK293 Cells; Humans; IL-2; Immunologic Factors - chemical synthesis; Immunologic Factors - chemistry; Immunologic Factors - pharmacology; Isoxazaoline; Isoxazoles - chemistry; Isoxazoles - pharmacology; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - immunology; Male; Mice; Middle Aged; Mitogenecity; Molecular Structure; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - immunology; Rats; Salicylic acid; Salicylic Acid - chemistry; Salicylic Acid - pharmacology; Spleen - drug effects; Spleen - immunology; Structure-Activity Relationship; Young Adult
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.02.052

Mitogenicity is the ability of the natural or synthetic compounds to induce cell division or proliferation. A series of salicylic acid derivatives containing isoxazoline moiety (8a-j) were synthesized and their immunopharmacological activities targeting lymphocyte proliferation and angiogenesis were evaluated. The compounds 8a-j mitogenicity were investigated on immunological cells that include human peripheral blood lymphocytes and murine splenocytes in-vitro. The results implicate that among the series of 8a-j, compound 8e showed a potent proliferative response on both human and murine lymphocytes. The proliferative index of the compound 8e was comparable to the reference mitogen Con A and mitogenecity is due to increased secretion IL-2. In -vivo CAM and rat corneal angiogenesis assays were performed to assess the compound's effect on endothelial cell migration and proliferation which inferred that 8e also induces the proliferation of endothelial cells. The study reports the synthetic immunostimulatory and pro-angiogenic activity of novel mitogen 8e which could be translated into new drug in future. [Display omitted] •Synthesis of salicylic acid fused isoxazoline analogues 8a-j via 1, 3-dipolar cycloaddition.•These synthesized compounds were characterized by spectral and analytical techniques.•Further, compounds (8a-j) were screened for biological applications.•Compound 8e showed a potent proliferative response on both human and murine lymphocytes.