Novel derivatives of 6-amino-2-phenylbenzothiazole bearing differentsubstituents (amino, dimethylamino or fluoro) on the phenyl ring were prepared as thecorresponding hydrochloride salts. 6-Nitro-2-(substituted-phenyl)benzothiazoles (1-6) weresynthesized by condensation reactions of substituted benzaldehydes with 2-amino-5-nitrothiophenol. Nitro derivatives were reduced to the amino derivatives with SnCl₂/HCl.Water soluble hydrochloride salts of 6-amino-2-(substituted-phenyl)benzothiazole (13-19)were prepared using concentrated or gaseous HCl. Compounds 13-19 were found to exertcytostatic activities against malignant human cell lines: cervical (HeLa), breast (MCF-7),colon (CaCo-2), laryngeal carcinoma (Hep-2), and normal human fibroblast cell lines (WI-38).

Newly designed and synthesized cyano, amidino and acrylonitrile 2,5-disubstituted furane derivatives with either benzimidazole/benzothiazole nuclei have been evaluated for antitumor and antimicrobial activity. For potential antitumor activity, the compounds were tested in 2D and 3D cell culture methods on three human lung cancer cell lines, A549, HCC827 and NCI-H358, with MTS cytotoxicity and BrdU proliferation assays in vitro. Compounds 5, 6, 8, 9 and 15 have been proven to be compounds with potential antitumor activity with high potential to stop the proliferation of cells. In general, benzothiazole derivatives were more active in comparison to benzimidazole derivatives. Antimicrobial activity was evaluated with Broth microdilution testing (according to CLSI (Clinical Laboratory Standards Institute) guidelines) on Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Additionally, Saccharomyces cerevisiae was included in testing as a eukaryotic model organism. Compounds 5, 6, 8, 9 and 15 showed the most promising antibacterial activity. In general, the compounds showed antitumor activity, higher in 2D assays in comparison with 3D assays, on all three cell lines in both assays. In natural conditions, compounds with such an activity profile (less toxic but still effective against tumor growth) could be promising new antitumor drugs. Some of the tested compounds showed antimicrobial activity. In contrast to ctDNA, the presence of nitro group or chlorine in selected furane-benzothiazole structures did not influence the binding mode with AT-DNA. All compounds dominantly bound inside the minor groove of AT-DNA either in form of monomers or dimer and higher-order aggregates.

A new synthetic strategy involving the Pinner reaction offers various amidino-functionalized 2-substituted benzoxazolesviaamidino-substituted 2-aminophenols with sub-micromolar antiproliferative activities.

Herein we present the synthesis of versatile amidino substituted benzothiazole 3–10 and benzimidazole 12–19 derivatives substituted with the variable number of hydroxy and methoxy groups. Furthermore, the synthesized compounds were explored for their antioxidative activity in vitro by using three biological assays, namely DPPH, ABTS and FRAP. The obtained results indicated that the variable number of hydroxy groups together with the type of the amidino substituent strongly influenced the antioxidative activity and reducing power of tested compounds. The most promising antioxidative activity showed trihydroxy substituted compounds 6, 10, 15 and 19. In general, it was noticed that unsubstituted amidino group induced the more pronounced activity in comparison to derivatives bearing 2-imidazolinyl group. This work is licensed under a Creative Commons Attribution 4.0 International License

We designed and synthesized a series of symmetric bis-6-amidino-benzothiazole derivatives with aliphatic central units and evaluated their efficacy against bloodstream forms of the African trypanosome Trypanosoma brucei. Of these, a dicationic benzothiazole compound (9a) exhibited sub-nanomolar in vitro potency with remarkable selectivity over mammalian cells (>26,000-fold). Unsubstituted 5-amidine groups and a cyclohexyl spacer were the crucial determinants of trypanocidal activity. In all cases, mice treated with a single dose of 20 mg kg^-1 were cured of stage 1 trypanosomiasis. The compound displayed a favorable in vitro ADME profile, with the exception of low membrane permeability. However, we found evidence that uptake by T. brucei is mediated by endocytosis, a process that results in lysosomal sequestration. The compound was also active in low nanomolar concentrations against cultured asexual forms of the malaria parasite Plasmodium falciparum. Therefore, 9a has exquisite cross-species efficacy and represents a lead compound with considerable therapeutic potential.