ABSTRACT
Novel lipidated analogs of iridoids viz., Agnuside and Negundoside with different chain length were synthesized and tested for immune adjuvant activity in the presence of weak antigen ovalbumin. Based on in vitro assay, 6-O-palmitoyl Agnuside (AG-3) was further taken up for detailed in vivo activity and found to significantly enhance the production of anti OVA IgG titer, neutralizing antibody (IgG1 and IgG2a) titer as well as soluble mediators of a Th1 (IL-2, IFN-γ)/Th2 response (IL-4) and proliferation of T lymphocyte subsets (CD4/CD8) and co stimulatory molecules CD80/CD86. Furthermore, the SAR studies revealed that presence of acyl group at aglycon moiety of these iridoid glycosides is crucial for immune adjuvant activity.
Subject(s)
Adjuvants, Immunologic/pharmacology , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , Glucosides/pharmacology , Iridoid Glycosides/pharmacology , Adjuvants, Immunologic/chemical synthesis , Animals , Antigens/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Proliferation/drug effects , Cytokines/blood , Glucosides/chemical synthesis , Immunoglobulin G/blood , Iridoid Glycosides/chemical synthesis , Male , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Spleen/cytology , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunologyABSTRACT
A series of novel 4beta-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives were synthesized by employing Cu(I)-catalyzed click chemistry and evaluated for their anticancer activity against a panel of seven human cancer cell lines (HT-29, HCT-15, 502713, HOP-62, A-549, MCF-7, and SF-295). The compounds 9b, 9c, 9e, 9f, and 9h showed significant cytotoxic activities especially against HT-29, HCT-15, 502713 cell lines.
