Grupo de Investigación en Sustancias Bioactivas GISB, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia, Calle 70 No. 52-21, Medellín 050010, Colombia.
Grupo Medicina Molecular y de Translación, Facultad de Medicina, Universidad de Antioquia, Carrera 51 D No. 62-29, Medellín 050010, Colombia.
Molecules. 2023 Mar 13;28(6):2601. doi: 10.3390/molecules28062601.
Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for (48.06 ± 3.35%) and (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatment.
癌症是全球范围内导致死亡的主要原因之一，也是延长预期寿命的障碍。为了寻找具有流行病学相关性的新化疗治疗分子，从石蒜科物种中测试了十种生物碱馏分对六种癌细胞系（AGS、BT-549、HEC-1B、MCF-7、MDA-MB 231 和 PC3）的作用，以 HaCat 作为对照细胞系。一些被确定为极度濒危且可用性极小的物种通过体外植物组织培养技术进行繁殖。进行了分子对接研究，以说明在涉及抗癌活性的一些分子靶标活性部位中鉴定出的 30 种石蒜科生物碱的结合取向，这些生物碱可能成为潜在的抗癌药物。在胃癌细胞系 AGS 中，在 30 µg/mL 时，（48.06 ± 3.35%）和 （45.79 ± 3.05%）获得了最佳结果（较低的细胞活力百分比）。研究集中在评估鉴定的生物碱对 Bcl-2 蛋白家族（Mcl-1 和 Bcl-xL）和 HK2 的影响，体外、计算和统计结果表明，粉防己碱和布福明碱可能具有细胞毒性活性。最后，将实验和理论测定相结合，使我们能够识别和表征潜在有用的癌症治疗生物碱。
