| In vitro: |
| Eur J Med Chem. 2010 Sep;45(9):4288-92. | | Synthesis and anticancer activity of chromone-based analogs of lavendustin A.[Pubmed: 20630626] |
Lavendustin A and hormothamnione were reported to exhibit cytotoxic effects on tumor cell lines.
METHODS AND RESULTS:
In the present studies, a series of chromone-based lavendustin analogs were synthesized as a simplified hybrid of hormothamnione and lavendustin A by the reductive-amination of formyl-chromone 5 with various amines followed by aminoalkylation.
CONCLUSIONS:
Most compounds synthesized showed significantly improved potencies compared to the standard compound 3 against most of cancer cell lines tested indicating that the removal of styryl group enhanced cancer cell growth inhibitory activities. Compound 4h and 4k showed the most potent inhibitory activities with GI(50) values in the range of 6.01-9.92 microg/ml on A-549 and HCT-15 cells. | | J Biol Chem. 1991 Nov 5;266(31):21105-12. | | Kinetic analysis of the inhibition of the epidermal growth factor receptor tyrosine kinase by Lavendustin-A and its analogue.[Pubmed: 1939153 ] | Lavendustin A was reported to be a potent tyrosine kinase inhibitor of the epidermal growth factor (EGF) receptor (Onoda, T., Iinuma, H., Sasaki, Y., Hamada, M., Isshibi, K., Naganawa, H., Takeuchi, T., Tatsuta, K., and Umezawa, K. (1989) J. Nat. Prod. 52, 1252-1257).
METHODS AND RESULTS:
Its inhibition kinetics was studied in detail using the baculovirus-expressed recombinant intracellular domain of the EGF receptor (EGFR-IC). Lavendustin A (RG 14355) is a slow and tight binding inhibitor of the receptor tyrosine kinase. The difference between the two values is due to the tight binding nature of the inhibitor to the enzyme in EI*. The kinetic analysis using a preincubation protocol to pre-equilibrate the enzyme with the inhibitor in the presence of one substrate showed that Lavendustin A is a hyperbolic mixed-type inhibitor with respect to both ATP and the peptide substrate, with a major effect on the binding affinities for both substrates.
CONCLUSIONS:
An analogue of Lavendustin A (RG 14467) showed similar inhibition kinetics to that of Lavendustin A. |
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