Molecular Bioprospection Department of Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Uttar Pradesh, India.
Curr Top Med Chem. 2020;20(21):1898-1909. doi: 10.2174/1568026620666200710103636.
Since centuries plant-based compounds are known for the treatment of cancer in both traditional and contemporary medicine. The problems like target non-specificity and toxicity are well-known regarding anticancer drugs. Therefore, target specific search of novel entities is constant. Isothymusin is a dimethoxy, trihydroxy flavone present in plants like Ocimum sanctum, and Limnophilla geoffrayi. There are limited reports available on the anticancer potential of isothymusin.
The effects of isothymusin on redox status, cell cytotoxicity, and targets involved in the promotion and progression of the cancer cells have been investigated.
Antiproliferative efficacy was evaluated by MTT, Neutral Red Uptake, and Sulforhodamine-B assays. The spectrophotometric methods were adopted to study the effect against selected targets. Redox activity was assessed by in vitro antioxidant assays and the interaction study, ADMET profiling, and toxicity assessments were done in silico.
Isothymusin scavenges the radicals, i.e., DPPH and nitric oxide with moderate ferric reducing potential. It affected the proliferation of leukemia, colon, skin, and breast cancer cell lines by more than 50% but moderately affected prostate, kidney, lung, hepatic, and breast adenocarcinoma (up to 48%). Isothymusin inhibited the enzymes associated with the promotion stage of cancer, including cycloxygenase- 2 and lipoxygenase-5. Additionally, it also inhibited the activity of proliferation markers like cathepsin- D, dihydrofolate reductase, hyaluronidase, and ornithine-decarboxylase. Besides, in silico studies supported the in vitro enzyme inhibition assays outcome. Toxicity studies showed promising results of chemical descriptors and non-skin-irritant, moderate ocular-irritancy, and in vitro Ames test confirmed non-mutagenic nature.
Isothymusin showed radical scavenging and anti-proliferative activities, which may be taken up as a phytochemical lead for the synthesis of analogues possessing enhanced anticancer potential.
几个世纪以来，植物化合物一直被用于传统和现代医学中的癌症治疗。然而，抗癌药物存在着靶点非特异性和毒性等问题。因此，人们一直在不断寻找具有特异性的新实体。异牡荆黄素是一种二甲氧基、三羟基黄酮，存在于圣罗勒和 Limnophilla geoffrayi 等植物中。关于异牡荆黄素的抗癌潜力，目前的报道有限。
研究了异牡荆黄素对氧化还原状态、细胞细胞毒性以及参与癌细胞促进和进展的靶点的影响。
通过 MTT、中性红摄取和磺基罗丹明 B 测定法评估抗增殖作用。采用分光光度法研究对选定靶点的作用。通过体外抗氧化测定和相互作用研究、ADMET 分析和毒性评估进行了氧化还原活性评估。
异牡荆黄素能清除自由基，如 DPPH 和一氧化氮，同时具有中等的铁还原能力。它对白血病、结肠、皮肤和乳腺癌细胞系的增殖有超过 50%的影响，但对前列腺、肾、肺、肝和乳腺腺癌的影响适度（高达 48%）。异牡荆黄素抑制与癌症促进阶段相关的酶，包括环氧化酶-2 和脂氧合酶-5。此外，它还抑制增殖标志物如组织蛋白酶-D、二氢叶酸还原酶、透明质酸酶和鸟氨酸脱羧酶的活性。此外，体内研究结果支持体外酶抑制试验的结果。毒性研究表明，化学描述符和非皮肤刺激性、中度眼部刺激性以及体外 Ames 试验结果具有良好的非致突变性。
异牡荆黄素表现出自由基清除和抗增殖活性，可作为合成具有增强抗癌潜力的类似物的植物化学先导物。
