# Diparlureas as Antitumor Agents
## 3 Other Diparlures
FCF treatment caused the suppression of HIF-1\(\alpha\) and HER2, both of them playing a crucial role in cancer cell survival [114]. Recently, several FCF analogues (UR214-1, UR214-7, and UR214-9) were demonstrated to be more effective in decreasing viability and proliferation in both ovarian and endometrial cancer cell lines, and suppress HER2 expression at a concentration lower than that of FCF. Moreover, FCF and its analogues were found to decrease the expression of human epididymis protein 4 (HE4), which is commonly upregulated in ovarian and endometrial cancers [115]. Diarylurea PQ401 is a small molecule that behaves as an inhibitor of IGF-1R signaling. It is also able to prevent breast cancer cells growth in in vivo mouse models [116]. It has also shown anti-cancer properties in glioma by inducing cellular apoptosis in US7 MG cells, thus reducing cell viability and proliferation and attenuating cell mobility in vitro. Moreover, through a mouse xenograft model, PQ401 administration led to the suppression of glioma tumor growth in vivo in mice [117]. Recently, PQ401 potential as a putative chemotherapy drug in osteosarcoma cells has been investigated. PQ401 effectively suppressed osteosarcoma cell growth, migration, and colony formation in vitro, as well as induced apoptosis in vitro. PQ401 inhibited U2 OS cell viability almost as effective as _cis_platin. PQ401 can significantly cause U2 OS cell apoptosis and clonogenesis at the IC\({}_{50}\) concentration with the blockade of IGF1-R phosphorylation and related downstream signaling [118]. The diphenyl urea-derivative DUD was designed on the basis of a docking study for the optimization of a natural product, taspine. The anti-metastatic potential of DUD for NSCLC was studied in vitro. DUD inhibited A549 cells migration by reversing EMT via Wnt/\(\beta\)-catenin and PI3K/Akt signaling, thus it has been suggested as a potential therapy for NSCLC treatment [119]. Several fluorinated diaryllureas were studied as activators of adenosine monophosphate-activated kinase (AMPK). Compound FND-4b determined the induction of phosphorylated AMPK and the decrease in markers of cell proliferation, as cyclin D1, in all CRC cell lines. Apoptosis was also increased in CRC cells treated with FND-4b [120]. Thidiazuron (TDZ, 1-phenyl-3-(1,2,3-thiadiazol-5-yl)) urea is a synthetic plant hormone which has been widely used as herbicide, pesticide, and as growth regulator in plant tissue culture [121]. Given its cytotoxic effect on HeLa (human-cervical carcinoma) cell lines, it has been recently proposed as a potential agent to act against cervical cancer cells. It has also suggested to have a role on apoptosis in cancer cells through DNA damage. Furthermore, the activity of TDZ as anticancer was tested against Hela cells by mitochondrial dysfunction, DNA damage, in silico caspase-3 inhibition, and some gene expression [122]. This observation has been recently confirmed by radiolabeling TDZ with 99 mTc. The in silico study supported the ability of 99 mTc-TDZ complex to bind caspase-3 protein that is overexpressed in cancers, suggesting that 99 mTc-TDZ might be a potential agent for diagnosis of solid tumors, such as the cervix cancer [123]. \begin{table}
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**Structure** & **