Recent progress in agents targeting polo-like kinases: Promising therapeutic strategies.

Polo-like kinases (PLKs) play important roles in regulating multiple aspects of cell cycle and cell proliferation. In many cancer types, PLK family members are often dysregulated, which can lead to uncontrolled cell proliferation and aberrant cell division and has been shown to associate with poor prognosis of cancers. The key roles of PLK kinases in cancers lead to an enhanced interest in them as promising targets for anticancer drug development. In consideration of PLK inhibitors and some other anticancer agents, such as BRD4, EEF2K and Aurora inhibitors, exert synergy effects in cancer cells, dual-targeting of PLK and other cancer-related targets is regarded as an rational and potent strategy to enhance the effectiveness of single-targeting therapy for cancer treatment. This review introduces the PLK family members at first and then focuses on the recent advances of single-target PLK inhibitors and summarizes the corresponding SARs of them. Moreover, we discuss the synergisms between PLK and other anti-tumor targets, and sum up the current dual-target agents based on them.

Synthesis and bioactivity evaluation of rhodanine derivatives as potential anti-bacterial agents.

Five series of (Z)-5-(4-(2-oxo-2-phenylethoxy)benzylidene)-2-thioxothiazolidin-4-one derivatives (I-V) were synthesized, characterized, and evaluated for their anti-bacterial activity. Most of the synthesized compounds showed potent inhibition against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with MIC values in the range of 1-32 µg/mL. Compounds IIIi, Vb and Vc presented the most potent activity, showing four-fold more potency than norfloxacin (MIC = 8 µg/mL and 4 µg/mL) and 64-fold more activity than oxacillin (MIC > 64 µg/mL) against MRSA CCARM 3167 and 3506 strains with MIC values of 1 µg/mL, and 64-fold more potency than norfloxacin (MIC > 64 µg/mL) and comparable activity to oxacillin (MIC = 1 µg/mL) against the QRSA CCARM 3505 and 3519 strains. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 µg/mL.