Novel benzo[b]thienyl and 2-bithienyl amidino-substituted benzothiazoles and benzimidazoles were shown to have antitumor and antitrypanosomal activities in vitro. Benzothiazoles were found to be more active than benzimidazole analogs as both antiproliferative and antitrypanosomal agents. Benzothiazoles were selective against lung carcinoma cells, and the benzimidazoles were selective against cervical carcinoma cells. The benzimidazoles target DNA, the benzothiazoles have a different cellular target.

Abstract

Novel benzo[b]thienyl- and 2,2′-bithienyl-derived benzothiazoles and benzimidazoles were synthesized to study their antiproliferative and antitrypanosomal activities in vitro. Specifically, we assessed the impact that amidine group substitutions and the type of thiophene backbone have on biological activity. In general, the benzothiazole derivatives were more active than their benzimidazole analogs as both antiproliferative and antitrypanosomal agents. The 2,2′-bithienyl-substituted benzothiazoles with unsubstituted and 2-imidazolinyl amidine showed the most potent antitrypanosomal activity, and the greatest selectivity was observed for the benzimidazole derivatives bearing isopropyl, unsubstituted and 2-imidazolinyl amidine. The 2,2′-bithiophene derivatives showed most selective antiproliferative activity. Whereas the all 2,2′-bithienyl-substituted benzothiazoles were selectively active against lung carcinoma, the benzimidazoles were selective against cervical carcinoma cells. The compounds with an unsubstituted amidine group also produced strong antiproliferative effects. The more pronounced antiproliferative activity of the benzothiazole derivatives was attributed to different cytotoxicity mechanisms. Cell cycle analysis, and DNA binding experiments provide evidence that the benzimidazoles target DNA, whereas the benzothiazoles have a different cellular target because they are localized in the cytoplasm and do not interact with DNA.

Over the past two decades, lysyl oxidases have been recognised as key enzymes in tumour invasion and metastasis, which has spurred efforts to develop inhibitors and molecular probes for therapeutic and imaging purposes, respectively. This review summarises the structural and functional aspects of these unique enzymes in relation to tumour progression and highlights recent developments in inhibitors and imaging probes.

Abstract

The understanding of the contribution of the tumour microenvironment to cancer progression and metastasis, in particular the interplay between tumour cells, fibroblasts and the extracellular matrix has grown tremendously over the last years. Lysyl oxidases are increasingly recognised as key players in this context, in addition to their function as drivers of fibrotic diseases. These insights have considerably stimulated drug discovery efforts towards lysyl oxidases as targets over the last decade. This review article summarises the biochemical and structural properties of theses enzymes. Their involvement in tumour progression and metastasis is highlighted from a biochemical point of view, taking into consideration both the extracellular and intracellular action of lysyl oxidases. More recently reported inhibitor compounds are discussed with an emphasis on their discovery, structure-activity relationships and the results of their biological characterisation. Molecular probes developed for imaging of lysyl oxidase activity are reviewed from the perspective of their detection principles, performance and biomedical applications.

The Front Cover illustrates pulmonary fungal infection caused by Cryptococcus species. Pathogenic fungi are eukaryotes and structurally similar to human cells, thus making it challenging to develop target-specific antifungal agents. The emergence of drug-resistant fungi has also created a need for novel classes of antifungal therapeutics. Tetrazole-backbone-containing compounds may be novel antifungal drugs with distinct mechanisms against cryptococcosis. Cover design by Nana Nakada and Taiga Miyazaki with special technical support from Rie Matsuura. More information can be found in the Research Article by Nana Nakada, Taiga Miyazaki et al..

In this review, we shed light on how the shapes of the glyco-nanostructures govern cell-specific homing and immune responses. We examine recent advances in glyco-nanostructures of various shapes that modulate carbohydrate–protein interactions. We specifically emphasize glyco-nanostructures constructed from small-molecule amphiphilic carbohydrates, block copolymers, metal-based nanoparticles, and carbon-based materials, highlighting their potential applications in glycobiology.

Abstract

Carbohydrate–protein interactions (CPIs) play a crucial role in the regulation of various physiological and pathological processes within living systems. However, these interactions are typically weak, prompting the development of multivalent probes, including nanoparticles and polymer scaffolds, to enhance the avidity of CPIs. Additionally, the morphologies of glyco-nanostructures can significantly impact protein binding, bacterial adhesion, cellular internalization, and immune responses. In this review, we have examined the advancements in glyco-nanostructures of different shapes that modulate CPIs. We specifically emphasize glyco-nanostructures constructed from small-molecule amphiphilic carbohydrates, block copolymers, metal-based nanoparticles, and carbon-based materials, highlighting their potential applications in glycobiology.