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2,2'-Thio-bis(4,6-dichlorophenol), namely bithionol, is a small molecule endowed with a multifaceted bioactivity. Its peculiar polychlorinated phenolic structure makes it a suitable candidate to explore its potentialities in establishing interaction patterns with enzymes of MedChem interest, such as the human carbonic anhydrase (hCA) metalloenzymes. Herein, bithionol was tested on a panel of specific hCAs through the stopped-flow technique, showing a promising micromolar inhibitory activity for the hCA II isoform. X-ray crystallographic studies revealed an unprecedented halogen-bond interaction between one chlorine of bithionol and the N3(ε) atom of the hCA II catalytically active histidine residue, His64. Then, quantum mechanics calculations based on the fragment molecular orbital method allowed us to estimate the strength of this bond (~2.9 kcal/mol) and highlighted the contribution of a rich hydrophobic interaction network within the isoenzyme. Interestingly, the compound inactivity against the hCA III isoform, characterized by His64Lys and Leu198Phe mutations, supported the key role played by halogen bonding in the enzyme affinity. This finding might pave the way for the development of a new class of hCA inhibitors characterized by such chemical features, with the halogen bond being a key ligand-receptor interaction., (© 2025 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Background & Aims: The relation between various types of plant-based diets and cancer risk is still unclear. We examined the association of the overall plant-based diet index (PDI) and healthy (hPDI) and unhealthy plant-based diet indices (uPDI) with the risk of selected digestive cancers., Methods: We used data from a network of hospital-based case-control studies including 942 oral/pharyngeal, 304 esophageal, 230 stomach, 1953 colorectal, and 326 pancreatic cancer cases. We calculated PDI, hPDI, and uPDI from a validated food frequency questionnaire. We used multivariable logistic regression models to estimate the odds ratios (OR) of selected digestive cancers across the three indices (in quintiles, Q, or tertiles, T, and in continuous)., Results: The PDI was significantly inversely associated with oral/pharyngeal (OR Q5 vs Q1 =0.63, 95% confidence interval, CI, 0.47-0.84) and esophageal cancer risk (OR T3 vs T1 =0.47, 95% CI 0.31-0.72). The inverse associations appeared stronger for the hPDI (oral cavity/pharynx: OR Q5 vs Q1 =0.52; 95% CI 0.39-0.70; esophagus: OR T3 vs T1 =0.59, 95% CI 0.39-0.91; stomach: OR T3 vs T1 =0.42, 95% CI 0.27-0.67; colorectum: OR Q5 vs Q1 =0.69; 95% CI 0.57-0.84; pancreas: OR T3 vs T1 =0.60; 95% CI 0.41-0.89). In contrast, the uPDI was directly associated with the risk of oral/pharyngeal (OR Q5 vs Q1 =1.43, 95% CI 1.06-1.94), colorectal (OR Q5 vs Q1 =2.28, 95% CI 1.86-2.81), and pancreatic cancer (OR T3 vs T1 =1.74, 95% CI 1.14-2.65). Esophageal and stomach cancer risks were non-significantly increased by 34% and 46% respectively in the highest uPDI quantile., Conclusion: A plant-based diet, especially a healthy plant-based diet, may reduce the risk of various digestive cancers, whereas an unhealthy plant-based diet may increase the risk. The quality of plant-based diets is important for digestive cancer risk evaluation and prevention., Competing Interests: Conflict of interest LSAA is a founding member and CLV a member of the International Carbohydrate Quality Consortium (ICQC). LSAA has received honoraria from the Nutrition Foundation of Italy (NFI). All other authors: no conflict of interest are reported., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)