- Virtual screening of National Cancer Institute database for claudin-4 inhibitors: Synthesis, biological evaluation, and molecular dynamics studies
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Claudin-4 (CLDN4) is a vital member of tight-junction proteins that is often overexpressed in cancer and other malignancies. The three-dimensional structure of human CLDN4 was constructed based on homology modeling approach. A total of 265 242 molecules from the National Cancer Institute (NCI) database has been utilized as a dataset for this study. In the present work, structure-based virtual screening is performed with the NCI database using Glide. By molecular docking, 10 candidate molecules with high scoring functions, which binds to the active site of CLDN4 were identified. Subsequently, molecular dynamics simulations of membrane protein were used for optimization of the top-three lead compounds (NCI110039, NCI344682, and NCI661251) with CLDN4 in a dynamic system. The lead molecule from NCI database NCI11039 (purpurogallin carboxylic acid) was synthesized and cytotoxic properties were evaluated with A549, MCF7 cell lines. Our docking and dynamics simulations predicted that ARG31, ASN142, ASP146, and ARG158 as critically important residues involved in the CLDN4 activity. Finally, three lead candidates from the NCI database were identified as potent CLDN4 inhibitors. Cytotoxicity assays had proved that purpurogallin carboxylic acid had an inhibitory effect towards breast (MCF7) and lung (A549) cancer cell lines. Computational insights and in vitro (cytotoxicity) studies reported in this study are expected to be helpful for the development of novel anticancer agents.
- Rambabu, Majji,Jayanthi, Sivaraman
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- ANTI-OBESITY AGENT COMPRISING COMPOUND CONTAINING BENZOTROPOLONE RING
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The object of the present invention is to provide an anti-obesity agent which contains a tea-derived component and which is safe and does not compromise the flavor of foods and beverages. According to the present invention, a safe and palatable anti-obesity agent can be provided by incorporating a benzotropolone ring-containing compound which has tea-derived, high inhibitory activities against lipase and alfa-glucosidase. The anti-obesity agent of the present invention does not compromise the flavor of foods and beverage, has palatability, and can be used in various use applications including foods and beverages intended for health enhancement such as reduction in triglycerides.
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Page/Page column 11
(2012/03/27)
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- Benzotropolone derivatives and modulation of inflammatory response
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The present invention provides novel benzotropolone derivatives represented by the general formula: 1 including neotheaflavate B and EGCGCa. The benzotropolone derivatives of the present invention are effective antioxidant and anti-inflammatory agents. The present invention also provides novel method of synthesizing benzotropolone compounds in high yields and method of treating inflammatory conditions using benzotropolone containing compounds.
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Page/Page column 10
(2008/06/13)
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- Enzymatic synthesis of tea theaflavin derivatives and their anti-inflammatory and cytotoxic activities
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Derivatives based on a benzotropolone skeleton (9-26) have been prepared by the enzymatic coupling (horseradish peroxidase/H2O2) of selected pairs of compounds (1-8), one with a vic-trihydroxyphenyl moiety, and the other with an ortho-dihydroxyphenyl structure. Some of these compounds have been found to inhibit TPA-induced mice ear edema, nitric oxide (NO) synthesis, and arachidonic acid release by LPS-stimulated RAW 264.7 cells. Their cytotoxic activites against KYSE 150 and 510 human esophageal squamous cell carcinoma and HT 29 human colon cancer cells were also evaluated.
- Sang, Shengmin,Lambert, Joshua D.,Tian, Shiying,Hong, Jungil,Hou, Zhe,Ryu, Jae-He,Stark, Ruth E.,Rosen, Robert T.,Huang, Mou-Tuan,Yang, Chung S.,Ho, Chi-Tang
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p. 459 - 467
(2007/10/03)
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