Anti-inflammatory properties of convolutamydine A and two structural analogues

• Published in: Life sciences (1973) 2014-10, Vol.116 (1), p.16-24
• Main Authors: Fernandes, Patricia D., Zardo, Renata S., Figueiredo, Gabriella S.M., Silva, Bárbara V., Pinto, Angelo C.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-inflammatory drugs; Behavior, Animal - drug effects; Carrageenan - toxicity; Cell Line; Convolutamydine A; Cyclooxygenase 2 - metabolism; Cytokines - metabolism; Dinoprostone - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Formaldehyde - pharmacology; Inflammation; Inflammation - drug therapy; Inflammation - pathology; Interleukin-6 - metabolism; Isatin; Isatin - analogs & derivatives; Isatin - chemical synthesis; Isatin - chemistry; Isatin - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Male; Marine; Mice; Mice, Inbred BALB C; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2014.08.019

Convolutamydine A is an oxindole alkaloid that can be isolated from a marine bryozoan. Due to the variety of biological effects, two analogues were synthesized and their anti-inflammatory properties were evaluated. The anti-inflammatory effects of convolutamydine A and its analogues (ISA003 and ISA147) were investigated in a formalin-induced licking behaviour model, where mice received an intraplantar injection of formalin and their licking behaviour was evaluated for 30min. Additionally, inflammatory parameters were evaluated in a subcutaneous air pouch (SAP) model of carrageenan-induced inflammation. Exudates were collected for leukocyte counts; measurement of protein, prostaglandin E2 (PGE2) and cytokines by ELISA; and analysis of nitric oxide (NO) using a nitrate conversion protocol. Cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (iNOS) from RAW 264.7 cells were quantified by immunoblotting. Convolutamydine A and its two analogues inhibited the formalin-induced licking response at doses as low as 0.01mg/kg. An inhibitory effect was also observed on leukocyte migration and the production of NO, PGE2 and cytokines (IL-6 and TNF-α). The reduction in inflammatory parameters did not appear to be correlated with a direct reduction in the number of cells in the SAP, because a reduction in NO and PGE2 production by cultured macrophages was observed in addition to the inhibition of iNOS and COX2 enzyme expression. These results indicate that convolutamydine A and its two analogues have significant anti-inflammatory effects. These substances can be improved to generate lead compounds for the synthesis of new anti-inflammatory drugs. [Display omitted]