1-Indanone

Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β-cyclodextrin.[Pubmed: 22885176 ]

Eur J Pharm Sci. 2012 Oct 9;47(3):596-603.

The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro.
METHODS AND RESULTS:
In this work, we investigated and compared for the first time the anti-HCV activity of two 1-Indanone TSCs, namely 5,6-dimethoxy-1-Indanone TSC and 5,6-dimethoxy-1-Indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects.
CONCLUSIONS:
The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models.

Oxidative potential of some endophytic fungi using 1-indanone as a substrate.[Pubmed: 22573162]

J Microbiol Biotechnol. 2012 Jun;22(6):832-7.

METHODS AND RESULTS:
The oxidative potential of the fungus Penicillium brasilianum, a strain isolated as an endophyte from a Meliaceae plant (Melia azedarach), was investigated using 1-Indanone as a substrate to track the production of monooxygenases. The fungus produced the dihydrocoumarin from 1-Indanone with the classical Baeyer-Villiger reaction regiochemistry, and (-)-(R)-3-hydroxy-1-Indanone with 78% ee. Minor compounds resulting from lipase and SAM activities were also detected. The biotransformation procedures were also applied to a collection of Penicillium and Aspergillus fungi obtained from M. azedarach and Murraya paniculata.
CONCLUSIONS:
The results showed that Baeyer-Villiger were mostly active in fungi isolated from M. azedarach. Almost all of the fungi tested produced 3-hydroxy-1-Indanone.

ChemMedChem. 2011 Aug 1;6(8):1485-94.

Synthesis, structural characterization, and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes: potential as antileukemic agents.[Pubmed: 21608131]

In the search for alternative chemotherapeutic strategies against leukemia, various 1-Indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1-Indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line.
METHODS AND RESULTS:
The crystal structure of [Pt(HL1)(L1)]Cl·2MeOH, where L1=1-Indanone thiosemicarbazone, was solved by X-ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity.
CONCLUSIONS:
Present findings show that, in U937 cells, 1-Indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies.