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Within this manuscript we present the design, synthesis and biological evaluation of novel benzazole derived acrylonitriles bearing bicyclic heteroaromatic rings. Either benzimidazole, benzothiazole or imidazo[4, 5-b]pyridine scaffolds are linked via acrylonitrile linker with different bicyclic heteroaromatics. All newly prepared are evaluated for their in vitro antiproliferative activity on 8 human cancer cells as well as on three human lung cancer cell lines in MTS citotoxicity and in BrdU proliferative assays performed on 2D and 3D assay format. Majority of tested compounds showed weak activity with the exception of naphthyl substituted benzimidazole derivative 13 and benzothiazolyl substituted derivative 17, both benzimidazole derived acrylonitriles. Also, as a promising compounds have proven to be imidazo[4, 5-b]pyridine derivatives 25 and 30 with selective activity against A549 cells. Furthermore, all compounds were tested for their antibacterial activity against nine bacteria strains and Saccharomyces cerevisiae. Only benzo[b]furan-2-yl substituted benzimidazole derivative 14 showed moderate activity.

A series of cyano- and amidino-substituted imidazo[4,5-b]pyridines were synthesized using standard methods of organic synthesis, and their biological activity was evaluated. Biological evaluation included in vitro assessment of antiproliferative effects on a diverse selection of human cancer cell lines, antibacterial activity against chosen Gram-positive and Gram-negative bacterial strains, and antiviral activity on a broad panel of DNA and RNA viruses. The most pronounced antiproliferative activity was observed for compound 10, which contained an unsubstituted amidino group, and compound 14, which contained a 2-imidazolinyl amidino group; both displayed selective and strong activity in sub-micromolar inhibitory concentration range against colon carcinoma (IC50 0.4 and 0.7 μM, respectively). All tested compounds lacked antibacterial activity, with the exception of compound 14, which showed moderate activity against E. coli (MIC 32 μM). Bromo-substituted derivative 7, which contained an unsubstituted phenyl ring (EC50 21 μM), and para-cyano-substituted derivative 17 (EC50 58 μM) showed selective but moderate activity against respiratory syncytial virus (RSV). ispartof: MOLECULES vol:28 issue:1 ispartof: location:Switzerland status: published

Imidazo-pyridines are important scaffold in organic and medicinal chemistry due to their promising biological activity. [1] Some of the derivatives have already found application in medicine, while many others are currently in clinical testing In this work, we have synthesized novel amidino-substituted derivatives of imidazo[4, 5-b]pyridine [2]. Main precursors for the synthesis of targeted derivatives were prepared by DMSO-mediated cyclization.[3] Unsubstituded amidines were prepared using lithium hexamethyldisilazane, while other were obtained by Pinner reaction.The structures of newly prepared compounds were confirmed by means of 1H and 13C NMR spectroscopy as well as MS spectrometry. All prepared compounds were evaluated for their antitumor activity in vitro on several human cancer cells as well as for their antiviral and antibacterial activity.

Benzazoles and coumarins are among the most privileged heterocyclic subunits in the medicinal chemistry due to their wide range of bioactivity. Iminocoumarine derivatives are known for their interesting spectroscopic properties as well as their application as fluorescent sensors. Monitoring pH range is crucial for studying many biological processes in live cell organelles. Conjugates of benzazoles and iminocoumarins are already being explored for pH sensing applications due to excellent spectroscopic response in correlation with pH value. This work presents the synthesis and spectroscopic characterization of novel iminocoumarine derived imidazo[4, 5- b]pyridines. Main percursor, 2- cyanomethylimidazo[4, 5-b]pyridine, was prepared in the cyclocondensation reaction with 2- cyanoacetamide, while targeted iminocoumarine derivatives were prepared in condensation with chosen 5-substituted salycil benzaldehydes. Nitro- substituted iminocoumarin was further condensed with 5-nitrosalycilbenzaldehid in order to explore additional conjugation on spectroscopic and pH sensing properties. The structures of newly prepared compounds were confirmed by means of 1H and 13C NMR spectroscopy as well as MS spectrometry. pH spectroscopic titrations will be performed in order to determine possible application as pH sensors in solutions followed by determination of pKa values experimentally as well as by computational approaches.