Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches

AKF-D52, a Synthetic Phenoxypyrimidine-Urea Derivative, Triggers Extrinsic/Intrinsic Apoptosis and Cytoprotective Autophagy in Human Non-Small Cell Lung Cancer Cells

“…Given that apoptosis inhibits cancer cell growth with minimal effects on normal cells, compounds that induce apoptosis might thus have potential utility in cancer treatment [ 39 ]. In a previous study, we found that AKF-D52 showed growth-inhibitory and cytotoxic effects on multiple cancer cell lines, including lung, colorectal, skin, ovarian, renal, prostate, breast, and hematologic cancers [ 26 ]. In the present study, we investigated the mechanisms underlying the antiproliferative effects of AKF-D52 at the molecular level, both in vitro and in vivo.…”

“…AKF-D52 ( Figure 1 A) was prepared as previously described [ 26 ]. Fetal bovine serum (FBS), penicillin/streptomycin (PS), Minimum Essential Medium (MEM), and RPMI 1640 medium were obtained from Life Technologies Inc (Chicago, IL, USA).…”

“…In a previous study, we found that a novel phenoxypyrimidine urea derivative, 1-(3,5-dimethoxyphenyl)-3-(4-(3-methoxyphenoxy)-2-((4-morpholinophenyl)amino)pyrimidin-5-yl)urea (AKF-D52), a diarylurea-2,4-disubstituted pyrimidine hybrid compound, showed antiproliferative properties in various cancer cells and inhibitory effect on multiple kinases, especially inhibition against Feline McDonough Sarcoma (FMS) and c-KIT. However, as the inhibition of the AKF-D52 on these protein tyrosine kinases is lower relative to sorafenib and pazopanib, it might only help to explain the evoked antiproliferative activity partially [ 26 ]. Notably, AKF-D52 induced apoptotic cell death in A549 lung cancer cells, but the molecular mechanisms underlying the growth inhibitory efficacy of AKF-D52 in human NSCLC cells have yet to be elucidated.…”

Pyrrolidine-based 3-deoxysphingosylphosphorylcholine analogs as possible candidates against neglected tropical diseases (NTDs): identification of hit compounds towards development of potential treatment of Leishmania donovani

“…Repurposing, reprofiling, repositioning, or redirecting are closely correlated terms that have been coined to describe the attempt to deploy compound(s) for targeting a certain pathological condition(s) although originally they are/were used; developed to be used or failed the process of development to be used for another disease(s) [6][7][8][9][10] . Although such a strategy towards drug discovery and development was previously known, implemented, and indeed, resulted in successful discoveries, the current global threats because of pandemic COVID-19 increased the awareness and sparked more interest in this strategy.…”

Design, Synthesis and Fungicidal Activity of Novel 2‐aryl‐thiazole Derivatives Containing Saccharin Motif

“…[1] Nowadays, there have been many successful cases of obtaining active molecules via molecular hybridization strategy. [2][3][4][5][6][7] Thiazole matrices play a prominent role in drug design, [8][9][10] as they feature high flexibility in location of substituents, i. e. substituents can be introduced at positions C-2, C-4 and, C-5. Moreover, by virtue of prominent bioactivities of various thiazole derivatives, thiazole ring has drawn tremendous attention in agrochemistry.…”