No abstract

We synthesize various substituted triazole-containing flavonoids and identify potent, nontoxic, and highly selective BCRP inhibitors. Ac18Az8, Ac32Az19, and Ac36Az9 possess m-methoxycarbonylbenzyloxy substitution at C-3 of the flavone moiety and substituted triazole at C-4′ of the B-ring. They show low toxicity (IC50 toward L929 > 100 μM), potent BCRP-inhibitory activity (EC50 = 1–15 nM), and high BCRP selectivity (BCRP selectivity over MRP1 and P-gp > 67–714). They inhibit the efflux activity of BCRP, elevate the intracellular drug accumulation, and restore the drug sensitivity of BCRP-overexpressing cells. Like Ko143, Ac32Az19 remarkably exhibits a 100% 5D3 shift, indicating that it can bind and cause a conformational change of BCRP. Moreover, it significantly reduces the abundance of functional BCRP dimers/oligomers by half to retain more mitoxantrone in the BCRP-overexpressing cell line and that may account for its inhibitory activity. They are promising candidates to be developed into combination therapy to overcome MDR cancers with BCRP overexpression.

This paper examines both theory and empirical evidence on the relationship between market concentration and profitability in Hong Kong's land market. Such a relationship has been the subject of substantial debate among academics and practitioners. The study highlights several distinctive characteristics of property development in Hong Kong, and particularly various competitive strategies. In Hong Kong, land can be acquired through public auction, redevelopment and lease modifications. Thus, those developers without a sufficient land bank tend to be very aggressive in land auction. However, in the land auction market, competition is keen and the land acquired expensive. This study found that the leading property developers do not take the largest share in the land auction market. We argue that the developers tend to locate themselves in a suitable market position or strategic domain, within which they sustain competitiveness by increasing their market share. We also found that the property developers undertaking a relatively high proportion of large-scale projects tend to have a higher proportion of profits from such projects.