Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents.
Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents.
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DOI：
10.1038/s41598-020-74572-1
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发表时间：
2020-10-21
影响因子：
4.6
通讯作者：
Mereddy VR
中科院分区：
文献类型：
--
作者：
Solano LN;Nelson GL;Ronayne CT;Jonnalagadda S;Jonnalagadda SK;Kottke K;Chitren R;Johnson JL;Pandey MK;Jonnalagadda SC;Mereddy VR
基于N-苯基吲唑的新型二芳基脲类化合物被设计、合成并评价为潜在的抗癌药物。这些衍生物的体外细胞活力研究表明，在几种癌细胞系（包括鼠转移性乳腺癌4 T1、鼠胶质母细胞瘤GL 261、人三阴性乳腺癌MDA-MB-231、人胰腺癌MIAPaCa-2和人结直肠癌细胞系WiDr）中具有良好的效力，IC 50值在0.4-50 μM范围内。对先导化合物8i中的酯基进行修饰以引入氨基酰胺以增加溶解度和稳定性，同时保留生物活性。进一步的体外研究表明，铅候选抑制管长度在HUVEC细胞。体内全身毒性研究表明，这些候选化合物在小鼠中耐受良好，没有任何显著的副作用。在WiDr肿瘤异种移植物和4 T1肿瘤同系移植物模型中的抗癌功效研究证明，先导候选物11在这些肿瘤模型中作为单一药剂表现出显著的抗肿瘤性质。
Novel N-phenylindazole based diarylureas have been designed, synthesized and evaluated as potential anticancer agents. In vitro cell viability studies of these derivatives illustrate good potency with IC50 values in the range of 0.4–50 μM in several cancer cell lines including murine metastatic breast cancer 4T1, murine glioblastoma GL261, human triple negative breast cancer MDA-MB-231, human pancreatic cancer MIAPaCa-2, and human colorectal cancer cell line WiDr. The ester group in the lead compound 8i was modified to incorporate amino-amides to increase solubility and stability while retaining biological activity. Further in vitro studies reveal that lead candidates inhibit tube length in HUVEC cells. In vivo systemic toxicity studies indicate that these candidate compounds are well tolerated in mice without any significant side effects. Anticancer efficacy studies in WiDr tumor xenograft and 4T1 tumor syngraft models demonstrate that the lead candidate 11 exhibits significant antitumor properties as a single agent in these tumor models.
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影响因子：
9.8
作者：
Ramjiawan RR;Griffioen AW;Duda DG
通讯作者：
Duda DG
DOI：
10.1200/jco.2007.15.9566
发表时间：
2008-10-10
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Cohen EE;Rosen LS;Vokes EE;Kies MS;Forastiere AA;Worden FP;Kane MA;Sherman E;Kim S;Bycott P;Tortorici M;Shalinsky DR;Liau KF;Cohen RB
通讯作者：
Cohen RB
影响因子：
3.4
作者：
Gou, Hong-Feng;Zhou, Lei;Chen, Xin-Chuan
通讯作者：
Chen, Xin-Chuan
影响因子：
1.8
作者：
Soriano, Perry A.;Liu, Nian;Wagman, Lawrence D.
通讯作者：
Wagman, Lawrence D.
影响因子：
4.1
作者：
Garuti, Laura;Roberti, Marinella;Ferraro, Mariarosaria
通讯作者：
Ferraro, Mariarosaria