Potential 2,4-dimethyl-1H-pyrrole-3-carboxamide bearing benzimidazole template: Design, synthesis, in vitro anticancer and in silico ADME study.

含有苯并咪唑模板的潜在 2,4-二甲基-1 h-吡咯-3-甲酰胺: 设计、合成、体外抗癌和计算机模拟研究。

  • 影响因子:3.88
  • DOI:10.1016/j.bioorg.2020.103660
  • 作者列表:"Rasal NK","Sonawane RB","Jagtap SV
  • 发表时间:2020-02-11

:A new series of 2,4-dimethyl-1H-pyrrole-3-carboxamide derivatives bearing benzimidazole moiety was synthesized through a molecular hybridization approach and evaluated for in vitro anticancer activity by NCI-60 on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancer cell lines at a single dose (10 µM). Among all the synthesized conjugates, some derivatives showed more or less good activity even at such a small dose, while, compound 5-(1H-benzo[d]imidazol-2-yl)-N-(1-cyclohexylethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (8f) displayed significant antiproliferative activity specifically against MDA-MB human cancer cell lines. Compound 8f showed promising activity against MDA-MB-435 cell line of melanoma (Growth inhibition: 62.46%) and MDA-MB-468 cell line of breast (Growth inhibition: 40.24%). Computational ADME study qualified its significant physicochemical, pharmacokinetic and drug-likeness properties with good predicted oral bioavailability. Thus this new hybrid molecules would be useful for further anticancer drug development.


: 通过分子杂交方法合成了一系列新的含有苯并咪唑基团的 2,4-二甲基-1 h-吡咯-3-甲酰胺衍生物,并通过 NCI-60 对白血病、黑色素瘤、肺、结肠、 CNS 、单剂量 (10 µ m) 的卵巢癌,肾癌,前列腺癌和乳腺癌细胞系。在所有合成的偶联物中,有些衍生物即使在如此小的剂量下也表现出或多或少的良好活性,而,化合物 5-(1 h-苯并 [d] imidazol-2-yl)-N-(1-环己基乙基) -2,4-二甲基-1 h-吡咯-3-甲酰胺 (8f) 对 MDA-MB 人癌细胞株表现出显著的抗增殖活性。化合物 8f 对黑色素瘤 MDA-MB-435 细胞株 (生长抑制: 62.46%) 和乳腺 MDA-MB-468 细胞株 (生长抑制: 40.24%) 显示出良好的活性。计算 ADME 研究证实了其显著的理化、药代动力学和药物相似性性质,预测的口服生物利用度良好。因此,这种新的杂化分子将有助于进一步的抗癌药物开发。



作者列表:["Abrahamsson H","Jensen BV","Berven LL","Nielsen DL","Šaltytė Benth J","Johansen JS","Larsen FO","Johansen JS","Ree AH"]

METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.

翻译标题与摘要 下载文献
作者列表:["Suvina V","Kokulnathan T","Wang TJ","Balakrishna RG"]

METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.

翻译标题与摘要 下载文献
来源期刊:Cancer letters
作者列表:["Zhou Z","Zhou Q","Wu X","Xu S","Hu X","Tao X","Li B","Peng J","Li D","Shen L","Cao Y","Yang L"]

METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.

翻译标题与摘要 下载文献