The natural product colchicine (Col) is a medication used to treat severe inflammatory conditions. Although its mechanism of action at the level of the cytoskeleton is known, its subcellular distribution has not yet been properly studied. In this work, we present the first rational approach to assess the intracellular localization and biological activity of this alkaloid. We conjugated Col to green-emitting BODIPY dyes (CBs) with alternative linkers of different lengths (CB1-CB12) via different types of linkages. Connections of Col with BODIPY generally reduced its cytotoxicity to different levels depending on the type of linker. From the analysis of CB effects on cytotoxicity, cell cycle, and tubulin polymerization, we selected the most potent substances for fluorescence microscopy. Treatment of cells with 10 μM conjugates for 15 h showed different effects on microtubule organization. Live-cell imaging revealed that CBs rapidly associated with cellular membranes. Double label experiments unveiled that the CB4, which was the most effective in inhibiting tubulin polymerization, binds to the endoplasmic reticulum (ER) and mitochondria. In silico modeling and SPR analyses confirmed the high potency of CB4 to bind to the colchicine site on tubulin.

• Klíčová slova
• BODIPY, cell-cycle, colchicine, cytotoxicity, flow-cytometry, fluorescence microscopy, in silico modeling, intracellular membranes, tubulin polymerization,
• Publikační typ
• časopisecké články MeSH

Advancements in small-molecule research have created the need for sensitive techniques to accurately study biological processes in living systems. Fluorescent-labeled probes have become indispensable tools, particularly those that use boron-dipyrromethene (BODIPY) dyes. Terpenes and terpenoids are organic compounds found in nature that offer diverse biological activities, and BODIPY-based probes play a crucial role in studying these compounds. Monoterpene-BODIPY conjugates have exhibited potential for staining bacterial and fungal cells. Sesquiterpene-BODIPY derivatives have been used to study sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), indicating their potential for drug development. Owing to their unique properties, diterpenes have been investigated using BODIPY conjugates to evaluate their mechanisms of action. Triterpene-BODIPY conjugates have been synthesized for biological studies, with different spacers affecting their cytotoxicity. Fluorescent probes, inspired by terpenoid-containing vitamins, have also been developed. Derivatives of tocopherol, coenzyme Q10, and vitamin K1 can provide insights into their oxidation-reduction abilities. All these probes have diverse applications, including the study of cell membranes to investigate immune responses and antioxidant properties. Further research in this field can help better understand and use terpenes and terpenoids in various biological contexts.

• MeSH
• fluorescenční barviva chemie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• sloučeniny boru * chemie   farmakologie   MeSH
• terpeny * chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene MeSH Prohlížeč
• fluorescenční barviva MeSH
• sloučeniny boru * MeSH
• terpeny * MeSH

The importance of natural products in medicine, and in particular, plant secondary metabolites used for the treatment of diseases and drug development, has been obvious for several thousands of years [...].

• Publikační typ
• úvodníky MeSH