Design, synthesis and anti-breast cancer properties of butyric ester tethered dihydroartemisinin-isatin hybrids.

Fifteen novel butyric ester tethered dihydroartemisinin-isatin hybrids 4a-d and 5a-k were designed, synthesized, and evaluated for cytotoxicity against four human breast cancer cell lines, including MCF-7, MDA-MB-231, MCF-7/ADR and MDA-MB-231/ADR using the MTT method. A significant part of them were active against the four tested cancer cell lines, and the representative hybrid 5b (IC50: 1.27 µM) was 14.88 -> 78.74 times more active than adriamycin (IC50: 18.90 µM), DHA (IC50: 28.28 µM) and ART (IC50: > 100 µM) against MCF-7 breast cancer cells, whereas hybrid 5c (IC50: 2.39 and 3.95 µM) was superior to adriamycin (IC50: 3.38 and >100 µM), DHA (IC50: 48.80 and 82.78 µM) and ART (IC50: >100 and >100 µM) against MDA-MB-231 and MDA-MB-231/ADR breast cancer cell lines. Moreover, the selected hybrids (IC50: >100 µM) displayed non-cytotoxicity towards normal MCF-10A breast cells, and the SI values of hybrids 5b,c were >78.74 and >41.84 respectively, demonstrating their excellent selectivity and safety profiles. Accordingly, hybrids 5b,c could serve as promising anti-breast cancer candidates and deserved further preclinical evaluations.

Benzofuran derivatives and their anti-tubercular, anti-bacterial activities.

Benzofuran is a fundamental structural unit in a variety of biologically active natural products, and its derivatives display various biological properties. Some benzofuran derivatives possess unique anti-tubercular and anti-bacterial action mechanism, and exhibit excellent in vitro and in vivo activities against both drug-sensitive and drug-resistant pathogens. Moreover, several benzofuran derivatives have already used in clinics for the treatment of various diseases. Thus, benzofuran is a useful pharmacophore to develop new anti-tubercular and anti-bacterial drugs. This review covers the recent advances of benzofuran derivatives as potential anti-tubercular and anti-bacterial agents, and the structure-activity relationship is also discussed to pave the way for the further rational development of this kind of derivatives.

Fluoroquinolone-isatin hybrids and their biological activities.

Hybridization of different pharmacophores from various bioactive substances into a single molecule is the potential weapon to prevent the drug resistance since this strategy can provide new leads with complimentary activities and/or multiple pharmacological targets. Fluoroquinolone and isatin are common pharmacophores, and their derivatives possess various biological activities. Obviously, hybridization of these two pharmacophores into one molecule may result in novel candidates with broader spectrum, higher efficiency, lower toxicity as well as multiple mechanisms of action. Therefore, fluoroquinolone-isatin hybrids have the potential for clinical deployment in the control and eradication of various diseases. This review covers the recent advances of fluoroquinolone-isatin hybrids as potential anti-bacterial, anti-tubercular, anti-viral and anti-cancer agents. The structure-activity relationship is also discussed to pave the way for the further rational development of this kind of hybrids.