de Souza Gabriela Alves, Chaves Lorrane de Souza, Velez Afonso Santine M M, Lacerda Jorge Lucas F, Pitasse-Santos Paulo, Santos Jayane Clys Conceição Dos, Chaves Otávio Augusto, Serpa Carlos, Valente Raphael do Carmo, da Fonseca Leonardo Marques, da Costa Santos Marcos André Rodrigues, Dos Reis Jhenifer Santos, Santos Carlos Antônio do Nascimento, Mendonça-Previato Lucia, Previato Jose Osvaldo, Freire-de-Lima Celio Geraldo, Decoté-Ricardo Debora, Freire-de-Lima Leonardo, Lima Marco Edilson Freire de
Departamento de Química Orgânica, Instituto de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.897-000, RJ, Brazil.
Programa de Pós-Graduação em Ciências Biológicas (Biofísica), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil.
Pharmaceuticals (Basel). 2025 Mar 24;18(4):456. doi: 10.3390/ph18040456.
Anticancer therapies represent the primary treatment option for a significant number of cancer patients globally; however, many of these treatments are associated with severe side effects as they target molecular structures present in both cancerous and healthy cells. In a similar context, the treatment of Chagas disease, a neglected tropical illness, is hindered by the high toxicity of the currently available drugs. Researchers are increasingly focusing on the development of safer and more selective alternatives, with natural compounds being studied as potential starting points for the creation of more effective drug candidates with a favorable therapeutic index. The aim of this study was to design simplified curcumin-derived structures that preserved or enhanced their therapeutic activity against human lung cancer cell lines and , while also improving bioavailability and minimizing toxicity. In this study, curcumin and two natural curcuminoids inspired the synthesis of a chalcone and a set of bis-chalcones, compound classes known for their enhanced stability compared with their natural parent derivatives. The synthetic strategy used was the acid-catalyzed aldol condensation reaction. The stability profiles, IC values against A549 and H460 tumor cell lines, and trypanocidal activity against amastigotes of these derivatives were assessed. The synthesized derivatives exhibited improved stability compared with the parent compounds, along with lower IC values in both A549 and H460 tumor cell lines. Additionally, one of the new analogs showed promising trypanocidal activity against amastigotes. This study provides a potential pathway toward the development of more effective and less toxic treatments for both cancer and Chagas disease. The simplified curcumin derivatives represent a promising foundation for designing new therapeutic agents with improved bioavailability and efficacy.
抗癌疗法是全球大量癌症患者的主要治疗选择；然而，这些治疗中的许多都伴有严重的副作用，因为它们靶向癌细胞和健康细胞中都存在的分子结构。在类似的背景下，恰加斯病（一种被忽视的热带疾病）的治疗受到现有药物高毒性的阻碍。研究人员越来越关注开发更安全、更具选择性的替代方案，天然化合物被作为潜在的起点进行研究，以创造出具有良好治疗指数的更有效候选药物。本研究的目的是设计简化的姜黄素衍生结构，这些结构保留或增强了它们对人肺癌细胞系的治疗活性，同时还提高了生物利用度并将毒性降至最低。在本研究中，姜黄素和两种天然姜黄素类似物启发合成了一种查尔酮和一组双查尔酮，与它们的天然母体衍生物相比，这些化合物类别以其增强的稳定性而闻名。所采用的合成策略是酸催化的羟醛缩合反应。评估了这些衍生物的稳定性概况、对A549和H460肿瘤细胞系的IC值以及对无鞭毛体的杀锥虫活性。与母体化合物相比，合成的衍生物表现出更高的稳定性，同时在A549和H460肿瘤细胞系中的IC值更低。此外，一种新的类似物对无鞭毛体显示出有前景的杀锥虫活性。这项研究为开发更有效、毒性更小的癌症和恰加斯病治疗方法提供了一条潜在途径。简化的姜黄素衍生物为设计具有改善的生物利用度和疗效的新型治疗药物奠定了有前景的基础。
