One-Pot Synthesis of Densely Substituted Pyrazolo[3,4‑<i>b</i>]‑4,7-dihydropyridines

We have achieved a facile synthesis of a combinatorial library of densely substituted pyrazolo­[3,4-<i>b</i>]-4,7-dihydropyridines the mimics of antigenital wart drug podophyllotoxinfrom 5-aminopyrazoles and 4-(methylthio) 4<i>H</i>-chromenes. The C(4) pyrazolyl 4<i>H</i>-chromenes, which also possess structural features of podophyllotoxin, were isolable intermediates in the two-step, one-pot condensation. The condensation took place in a one-pot, multicomponent manner when 3-oxo-3-phenylpropanenitriles, hydrazine (precursors for 5-aminopyrazoles) and 4-(methylthio)-4<i>H</i>-chromenes were heated in refluxing ethanol. The condensation, however, stops at 4<i>H</i>-chromene stage when methyl hydrazine or phenylhydrazine were employed. Our findings offer an opportunity for synthesis of a combinatorial library of podophyllotoxin mimics, thus paving the way for discovery of lead candidates for cancer treatment

The quorum sensing molecule <i>N</i>-acyl homoserine lactone produced by <i>Acinetobacter baumannii</i> displays antibacterial and anticancer properties

<p>Secretory <i>N</i>-acyl homoserine lactones (AHLs) mediate quorum sensing (QS) in bacteria. AHLs are shown to be inhibitory for an unrelated group of bacteria and might mimic host signalling elements, thereby subverting the regulatory events in host cells. This study investigated the AHL produced by <i>Acinetobacter baumannii</i> and analysed its effect on other bacterial species and mammalian cells. Chemically characterized AHL had an m/z value of 325 with a molecular formula C₁₈H₃₁NO₄ and showed its inhibitory potential against <i>Staphylococcus aureus</i>. Molecular docking studies identified D-alanine-D-alanine synthetase A, a cell wall synthesizing enzyme of <i>S. aureus</i> having a strong binding affinity towards AHL. Electron microscopy showed the disruption and sloughing off of the <i>S. aureus</i> cell wall when treated with AHL. <i>In vitro</i> experiments revealed that this bacteriostatic AHL showed time-dependent activity and induced apoptosis in cancer cell lines. This compound could be a potential structural backbone for constructing new AHL analogues against <i>S. aureus</i>. The findings emphasize the need to re-evaluate all previously characterized AHLs for any additional new biological functions other than QS.</p