title: Synthesis of α-santonin derivatives for diminutive effect on T and B-cell proliferation and their structure activity relationships.
abstract: A new library of 20 compounds from α-santonin was synthesized and tested against Con-A induced T-cell proliferation and LPS-induced B-cell proliferation via MTT assay. The study resulted in the identification of potent immunosuppressant molecules, which were further screened along with α-santonin for Tumor Necrosis Factor Alpha (TNF-α) inhibitory activity. One of the molecules (7) at 10 μM showed equipotency to that of dexamethasone (1 μM conc.) used as a standard. Structure activity relationships of the synthesized compounds along with our earlier reported α-santonin derivatives have been studied. Inferences from the modifications carried out at all the three sites of α-santonin have been elaborated. Computational study of the active compounds shows TNF-α protein as its preferable target rather than Inosine Monophosphate Dehydrogenase (IMPDH).
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Catalysis and Peptide Research Unit, University of KwaZulu-Natal, Durban, 4041, South Africa.
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: Jasvinder
authors.initials: J
authors.lastname: Singh
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Discovery Informatics, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Nargotra
authors.affiliation: Discovery Informatics, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Priya
authors.initials: P
authors.lastname: Mahajan
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Anupurna
authors.initials: A
authors.lastname: Kaul
authors.affiliation: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors.forename: Zabeer
authors.initials: Z
authors.lastname: Ahmed
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: skoul@iiim.ac.in.
authors.forename: Surrinder
authors.initials: S
authors.lastname: Koul
authors.affiliation: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: plsangwan@iiim.ac.in.
authors.forename: Payare L
authors.initials: PL
authors.lastname: Sangwan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D007168:IMP Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D012500:Santonin / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D012500:Santonin; D007168:IMP Dehydrogenase
keywords: ConA; Immunosuppressant; In silico study; LPS; T and B cell, SARs; α-Santonin