title: Synthesis of α-santonin derived acetyl santonous acid triazole derivatives and their bioevaluation for T and B-cell proliferation.
abstract: A new series of α-santonin derived acetyl santonous acid 1,2,3-triazole derivatives were synthesised using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their in vitro inhibition activity on concanavalin A (ConA) induced T cell proliferation and lipopolysaccharide (LPS) induced B cell proliferation. Among the synthesised series, compounds 2-10 and 19 exhibited significant inhibition against ConA and LPS stimulated T-cell and B-cell proliferation in a dose dependent manner. More significantly compounds 4, 9-10 and 19 exhibited potent inhibition activity with remarkably lower cytotoxicity on the mitogen-induced T cell and B cell proliferation at 1 μM concentration. The compound 6 displayed potent immunosuppressive effects with ∼89% against LPS induced B-cell and ∼83% against ConA stimulated T-cell proliferation at 100 μM concentration without cytotoxicity. Compound 10 was more selective against B cell proliferation and exhibited 81% and 69% suppression at 100 and 1 μM concentration respectively. The present study led to the identification of several santonin analogs with reduced cytotoxicity and strong inhibition activity against the cell proliferation induced by the mitogens.
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
authors.forename: Nisar A
authors.initials: NA
authors.lastname: Dangroo
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India.
authors.forename: Jasvinder
authors.initials: J
authors.lastname: Singh
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
authors.forename: Alamgir A
authors.initials: AA
authors.lastname: Dar
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Chinthakindi
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India.
authors.forename: Anpurna
authors.initials: A
authors.lastname: Kaul
authors.affiliation: University of Kashmir, Hazaratbal Road, Srinagar, India.
authors.forename: Mohmmed A
authors.initials: MA
authors.lastname: Khuroo
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IIIM Campus, Jammu, India. Electronic address: plsangwan@iiim.ac.in.
authors.forename: Payare L
authors.initials: PL
authors.lastname: Sangwan
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents; D012500:Santonin / Q000737:chemistry*; D013601:T-Lymphocytes / Q000166:cytology*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D014230:Triazoles; D012500:Santonin
keywords: ConA; Immunosuppresants; LPS; Santonous acid triazole; T and B cell; α-Santonin