title: Indenes and tetralenes analogues attenuates lipopolysaccharide-induced inflammation: An in-vitro and in-vivo study.
abstract: In an effort to evaluate novel pharmacological activity of 1-chloro-2-formyl indene and tetralene analogues possessing potential antitubercular and antistaphylococcal agents, we explored its anti-inflammatory potential against lipopolysaccharide(LPS)-induced inflammation using in-vitro and in-vivo bioassay. Synthesized analogues significantly inhibited the production and expression of pro-inflammatory cytokines against LPS-induced inflammation in macrophages isolated from mice. Among all the analogues, TAF-5 (1-Chloro-2-formyl-1-tetralene) exhibited most potent anti-inflammatory activity without any cytotoxic effect. We have further evaluated the therapeutic efficacy and safety of TAF-5 in in-vivo system using LPS-induced sepsis, a systemic inflammation model and acute oral toxicity respectively in mice. Oral administration of TAF-5 inhibited the pro-inflammatory cytokines in serum, attenuated the organs injuries and improved host survival in dose dependent manner. Acute oral toxicity study showed TAF-5 is non-toxic at higher dose in mice. These results suggest the suitability of indene and tetralene analogues as new chemical entities for further investigation towards the management of inflammation related diseases.
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Mohanty
authors.affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Yashveer
authors.initials: Y
authors.lastname: Gautam
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Maurya
authors.affiliation: Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India. Electronic address: as.negi@cimap.res.in.
authors.forename: Arvind S
authors.initials: AS
authors.lastname: Negi
authors.affiliation: Molecular and Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Om
authors.initials: O
authors.lastname: Prakash
authors.affiliation: Molecular and Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India. Electronic address: du.bawankule@cimap.res.in.
authors.forename: Dnyaneshwar Umrao
authors.initials: DU
authors.lastname: Bawankule
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007192:Indenes / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D062105:Molecular Docking Simulation; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007192:Indenes; D008070:Lipopolysaccharides
keywords: Indene; Inflammation; LPS; Macrophage; Mice; Sepsis; Tetralene