Scholarlink

Background <p>The convergence of microbial infections and cancer risk in inflammatory skin diseases demands novel, multi-functional therapeutics. This challenge is exacerbated by the rise in antimicrobial resistance and the lack of approved drugs for pathogens like human adenovirus (HAdV).</p> Methods <p>Here, we investigated a series of isoxazole derivatives to identify lead candidates with combined antibacterial, antiviral, and anticancer properties for dermatological applications. The tests performed include antibacterial agar diffusion assay, antiviral quantitative suspension test, in silico and in vitro assays such as MTT, Rho-123, DCF-DA, Griess, as well as ELISA tests (Caspase-3, IL-6, TNF-α, COX), and detection of apoptosis in a microchip.</p> Results <p>Our study identified compound <b>MO3</b> with significant antibacterial action against Staphylococcus aureus and the zoonotic pathogen Staphylococcus pseudintermedius. In antiviral assays, <b>MO10</b> and <b>MO7</b> demonstrated exceptionally high virucidal potency against HSV-1 (100-fold greater than the threshold) and AdV-5 (10-fold greater than the threshold), respectively, while remaining non-toxic to human fibroblasts. Critically, <b>MO10</b> also exhibited multi-modal anticancer effects in melanoma, inducing NO-mediated apoptosis, reducing pro-inflammatory cytokines, and acting in strong synergy with doxorubicin to enhance its chemotherapeutic effect.</p> Conclusion <p>In conclusion, this work validates specific isoxazole derivatives as highly promising candidates for development: <b>MO3</b> for resistant bacterial infections, <b>MO7</b> for otherwise untreatable adenovirus infections, and <b>MO10</b> as a dual-action agent against HSV-1 and an adjunct to melanoma chemotherapy.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Isoxazole derivatives as multi-target agents: virucidal, antibacterial, and antiproliferative effects on skin cancer cells

  • 期刊论文

  • 发表日期：

    2026年3月4日

查看全文
  • Izabela Jęśkowiak-Kossakowska,
  • Paulina Nowotarska,
  • Elżbieta Gębarowska,
  • Barbara Bażanów,
  • Tomasz Gębarowski,
  • Roman Szafran,
  • Aleksandra Chwirot,
  • Edward Krzyżak,
  • Adam Szeląg,
  • Marcin Mączyński,
  • Maciej Janeczek,
  • Benita Wiatrak

摘要

Background

The convergence of microbial infections and cancer risk in inflammatory skin diseases demands novel, multi-functional therapeutics. This challenge is exacerbated by the rise in antimicrobial resistance and the lack of approved drugs for pathogens like human adenovirus (HAdV).

Methods

Here, we investigated a series of isoxazole derivatives to identify lead candidates with combined antibacterial, antiviral, and anticancer properties for dermatological applications. The tests performed include antibacterial agar diffusion assay, antiviral quantitative suspension test, in silico and in vitro assays such as MTT, Rho-123, DCF-DA, Griess, as well as ELISA tests (Caspase-3, IL-6, TNF-α, COX), and detection of apoptosis in a microchip.

Results

Our study identified compound MO3 with significant antibacterial action against Staphylococcus aureus and the zoonotic pathogen Staphylococcus pseudintermedius. In antiviral assays, MO10 and MO7 demonstrated exceptionally high virucidal potency against HSV-1 (100-fold greater than the threshold) and AdV-5 (10-fold greater than the threshold), respectively, while remaining non-toxic to human fibroblasts. Critically, MO10 also exhibited multi-modal anticancer effects in melanoma, inducing NO-mediated apoptosis, reducing pro-inflammatory cytokines, and acting in strong synergy with doxorubicin to enhance its chemotherapeutic effect.

Conclusion

In conclusion, this work validates specific isoxazole derivatives as highly promising candidates for development: MO3 for resistant bacterial infections, MO7 for otherwise untreatable adenovirus infections, and MO10 as a dual-action agent against HSV-1 and an adjunct to melanoma chemotherapy.