Hamid A A, Kaushal Tanu, Ashraf Raghib, Singh Arjun, Chand Gupta Amit, Prakash Om, Sarkar Jayanta, Chanda Debabrata, Bawankule D U, Khan Feroz, Shanker Karuna, Aiyelaagbe O O, Negi Arvind S
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India; Department of Chemistry, University of Ilorin, Ilorin, Nigeria.
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Steroids. 2017 Mar;119:43-52. doi: 10.1016/j.steroids.2017.01.001. Epub 2017 Jan 28.
Prostate cancer is one of the most common cancers in men. Diosgenin and related compounds are potential cytotoxic agents. Twelve diverse analogues of long chain fatty acid/ester of diosgenin-7-ketoxime have been prepared. Six of the analogues exhibited significant anticancer activity against a panel of human cancer cell lines with IC ranging from 12 to 35μM. Compound 16, the best representative of the series exerted S phase arrest in DU145 prostate cancer cells and induced apoptosis through caspase pathway. Additionally, these analogues inhibited lipopolysaccharide induced pro-inflammatory cytokines (TNF-α and IL-6) up to 47.7% and 23.3% respectively. Compound 16 was found to be safe in acute oral toxicity in Swiss albino mice up to 300mg/kg dose. The anticancer and antiinflammatory properties of compound 16 are important and can further be optimized for a better anti-prostate cancer candidate.
前列腺癌是男性中最常见的癌症之一。薯蓣皂苷元及其相关化合物是潜在的细胞毒性剂。已制备了十二种不同的薯蓣皂苷元-7-酮肟长链脂肪酸/酯类似物。其中六种类似物对一组人类癌细胞系表现出显著的抗癌活性,IC范围为12至35μM。该系列中最具代表性的化合物16在DU145前列腺癌细胞中引起S期阻滞,并通过半胱天冬酶途径诱导细胞凋亡。此外,这些类似物分别将脂多糖诱导的促炎细胞因子(TNF-α和IL-6)抑制高达47.7%和23.3%。发现化合物16在瑞士白化小鼠中以高达300mg/kg的剂量进行急性口服毒性试验时是安全的。化合物16的抗癌和抗炎特性很重要,可以进一步优化以成为更好的抗前列腺癌候选药物。