title: Synthesis and anti-inflammatory activity of novel triazole hybrids of (+)-usnic acid, the major dibenzofuran metabolite of the lichen Usnea longissima.
abstract: (+)-Usnic acid ((R)-2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione), a dibenzofuran isolated from the lichen Usnea longissima, has been chemically transformed to synthesize a series of sixteen novel triazole analogs by click chemistry approach. The synthesized compounds were tested for their anti-inflammatory potential against the cytokines TNF-[Formula: see text] and IL-1[Formula: see text] in U937 cell lines. The bromo enamines (2a, 2b), azido enamines (3a, 3b) and triazole analogs (4f, 4g, 4h, 5f, 5g and 5h) exhibited promising anti-inflammatory activity against TNF-[Formula: see text] with [Formula: see text] values ranging from 1.40 to 5.70 [Formula: see text]M. Most significantly, the [Formula: see text] values of compounds 5f (1.40 [Formula: see text]M) and 5h (1.88 [Formula: see text]M) are the lowest among the compounds tested and found close to that of standard prednisolone. Hence, these two compounds can be considered as lead molecules for further fine tuning to make highly potent anti-inflammatory therapeutic agents.
authors.affiliation: Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.|Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India.
authors.forename: Nagi Reddy
authors.initials: NR
authors.lastname: Vanga
authors.affiliation: Pharmacology and Toxicology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Anudeep
authors.initials: A
authors.lastname: Kota
authors.affiliation: Pharmacology and Toxicology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India. sistla@iict.res.in.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
authors.affiliation: Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India. mallavadhani@iict.res.in.|Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad, 500007, India. mallavadhani@iict.res.in.
authors.forename: Mallavadhani
authors.initials: M
authors.lastname: Uppuluri
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry* / Q000378:metabolism*; D057930:Click Chemistry; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells; D020949:Usnea / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D053583:Interleukin-1beta; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C073339:usnic acid; C023614:dibenzofuran
keywords: Anti-inflammatory activity; Click chemistry; IL-1; TNF-; Triazoles; Usnic acid