Explore the vast range of titles available.

Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.

AbstractObjectivesTo assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3).DesignMulticentre, double blind, randomised, placebo controlled trial.Setting244 hospitals in China between 11 August 2022 and 13 April 2023.Participants8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled.InterventionsPatients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days.Main outcome measuresThe primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat.Results4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83).ConclusionsThe study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L.Trial registrationClinicalTrials.gov, NCT05439356.

Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, and clinically significant drug–drug interactions, partly mediated by modulation of P-glycoprotein and cytochrome P450 3A4 metabolism. This review explores advanced delivery strategies designed to overcome these limitations. We critically evaluate lipid-based systems, such as solid lipid nanoparticles, liposomes, transferosomes, ethosomes, and cubosomes; polymer-based nanoparticles; microneedles; and implants, including drug-eluting stents. These systems ensure targeted delivery, improve pharmacokinetics, and reduce toxicity. Additionally, we discuss chemical derivatization approaches, such as prodrugs, codrugs, and strategic ring modifications (A-, B-, and C-rings), aimed at optimizing both the efficacy and safety profile of colchicine. Combinatorial nanoformulations that enable the co-delivery of colchicine with synergistic agents, such as glucocorticoids and statins, as well as theranostic platforms that integrate therapeutic and diagnostic functions, are also considered. These innovative delivery systems and derivatives have the potential to transform colchicine therapy by broadening its clinical applications while minimizing adverse effects. Future challenges include scalable manufacturing, long-term safety validation, and the translation of research into clinical practice.

Patients with chronic coronary disease were randomly assigned to receive 0.5 mg of colchicine once daily or matching placebo. The incidence of the composite end point of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was significantly lower with colchicine than with placebo.

Inflammation appears to play a role in atherosclerosis, raising the possibility that treatments that reduce inflammation could prevent cardiovascular events. In a randomized, placebo-controlled trial involving 4745 patients with recent myocardial infarction, low-dose colchicine (0.5 mg once daily) prevented ischemic cardiovascular events.

This study highlights the potential of nanoparticle-encapsulated colchicine as a safer and more effective alternative to free colchicine for treating atherosclerotic vascular disease (ASCVD). While colchicine is known for its anti-inflammatory properties, its dose-dependent toxicity limits long-term clinical use. To address this issue, colchicine was encapsulated in polymeric nanoparticles synthesized through a microfluidic method using methylated β-cyclodextrin as the initiator. The resulting formulation achieved an encapsulation efficiency of 30% and a drug loading capacity of 75%, indicating a high payload capability. This approach not only demonstrated high drug-loading efficiency but also enabled controlled release, with approximately 60% of the drug being released over 96 h. The nanoparticle formulation preserved colchicine’s ability to inhibit foam cell formation—a critical event in the progression of atherosclerosis—while significantly reducing toxicity to eukaryotic cells. Transmission electron microscopy revealed that cells treated with nanoparticle-bound colchicine maintained normal morphology, unlike those exposed to free colchicine, which rapidly accumulates intracellularly and disrupts cell function. In vivo evaluation confirmed the safety of the formulation, showing no adverse effects on the liver, kidneys, or heart, as indicated by stable levels of ALT, AST, creatinine, and cardiac troponin I. Biodistribution studies with fluorescently labeled nanoparticles further suggested accumulation in tissues such as the heart and liver, highlighting the potential therapeutic relevance of colchicine-loaded nanoparticles for cardiovascular applications. Given these findings, the nanoparticle-based colchicine formulation presents a favorable efficacy and safety profile, warranting further preclinical development and eventual clinical evaluation.

Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).