non-invasive-endotracheal-administration-lipopolysaccharide-to-induce

Non-Invasive Endotracheal Administration of Lipopolysaccharide to Induce Acute Lung Injury in Rodents

Acute Lung Injury (ALI) is a life-threatening inflammatory condition characterized by arterial hypoxemia, alveolar edema, compromised ...

CSIR-Indian Institute of Integrative Medicine

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad-201002, India

Transient receptor potential vanilloid type 4 (TRPV4) is a versatile ion channel with diverse roles in immune cells, including macrophages. While its function in inflammation remains debated, we investigated its role in regulating IL-10 production and its impact on macrophage reprogramming during inflammation.

TRPV4 facilitates the reprogramming of inflamed macrophages by regulating IL-10 production via CREB.

Colchicine binds to tubulin and destabilizes microtubules, stopping cell division and causing apoptosis. Its anti-cancer property affects microtubule integrity despite its reported toxicity. A series of novel colchicine derivatives were synthesized using the multi-component reaction method and evaluated for their antiproliferative properties, aiming to enhance their efficacy as anti-cancer agents compared to the parent compound, colchicine. With the SRB assay, we tested these derivatives for their anti-cancer efficacy against lung, breast, and melanoma using several human cancer cell lines, including A549, MCF-7, MDAMB-231, and A375. The study identified a derivative, , as notably more effective against melanoma cells, with a selectivity index about two times higher than colchicine. We further investigated the anti-cancer efficacy of compound  on human melanoma cells using additional  models, including the wound healing assay and colony formation assay. Compound  inhibited colony formation by up to 62.5% and reduced the migration potential of melanoma cells by 69%. The  studies reveal the probable interactions with the colchicine binding sites that have a comparable pose to colchicine.  formed a hydrogen bond with Cys241, Asn258 and a salt bridge with Lys352, which is important for its tubulin polymerization inhibitory activity. These findings suggest that  could selectively target melanoma cells, minimizing toxicity to healthy cells and potentially providing a safer and more effective treatment option with improved therapeutic outcomes.

Article	Year
TRPV4 facilitates the reprogramming of inflamed macrophages by regulating IL-10 production via CREB. Inflammation research : official journal of the European Histamine Research Society ... [et al.]\| PubMed ID: 39101955	2024
Design, synthesis and antiproliferative activity of novel colchicine derivatives: selective inhibition of melanoma cell proliferation. Frontiers in pharmacology\| PubMed ID: 40657636	2025

Yassir Arfath

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