Coumarin-acetohydrazide derivatives as novel antiproliferative agents via VEGFR-2/AKT axis inhibition and apoptosis triggering

Abstract

The VEGFR-2/AKT pathway is a crucial axis in tumor survival where it is highly dysregulated in many cancer types. In this research, novel coumarin-acid hydrazides were synthesized and assayed for...

Novel 3-phenylquinazolin-2,4(1H,3H)-diones as dual VEGFR-2/c-Met-TK inhibitors: design, synthesis, and biological evaluation

“…4 ) 16 , 30 – 34 . The forth is a hydrophobic moiety (in purple) that occupies allosteric pocket of the TKs 3 , 4 , 6 , 35 .

Figure 3 HB domain requirements for dual VEGFR-2/c-Met TKs inhibition over VEGFR-2 single inhibition.

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Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases

“…Esculetin, a natural coumarin derivative, significantly slows the growth of prostate cancer by enhancing cell cycle arrest, modifying the PTEN/AKT signalling pathway, and inducing apoptosis via the EGFR/PI3K/Akt signalling pathway 23 , 24 . Several coumarin derivatives have been described in the literature as cytotoxic medicines for solid tumours as compounds I–IIIa,b that function as PI3K inhibitors ( Figure 1 ) 19 , 22 , 25 . On the other hand, compound IV has potent cytotoxicity on breast cancer due to binding interactions with the hydrophobic core of EGFR kinase 26 .…”

“…These novel agents were then tested as potential antineoplastic agents against PC-3 prostate cancer cells and MDA-MB-231 breast cancer cells. The anticancer characteristics of the coumarin-acetohydrazide hybrids IIb and IIIb produced in our earlier research study 25 served as the inspiration for series A ( Scheme 1 ) that formed through chain elongation with either a hydrazone (4a–5) or with thiosemicarbazide ( 6a–c ). In series B ( Scheme 2 ), the coumarin core’s cyclisation produced an amino triazole derivative 7 and it was then alkylated to form compound 8 .…”

Novel pyrazolo[3,4-d]pyrimidine derivatives: design, synthesis, anticancer evaluation, VEGFR-2 inhibition, and antiangiogenic activity

“…2 illustrates a selection of both marketed VEGFR-2 inhibitors (sunitinib and sorafenib) and previously published pyrazolo [3,4-d]pyrimidine derivatives (I-VI), which have exhibited promising anticancer activity and VEGFR-2 inhibitory effects. 29,[35][36][37][38][39] Building upon these findings and building on our previous research on anticancer derivatives, [40][41][42][43][44][45][46][47] specifically focusing on VEGFR-2 inhibitors, [48][49][50][51][52][53] the main objective of this study was to synthesize novel derivatives of pyrazolo [3,4-d]pyrimidine with anticancer activity, while possessing the fundamental pharmacophoric properties found in first-generation VEGFR-2 inhibitors such as sunitinib, through ring variation and bio isosteric replacement (Fig. 3).…”

“…Building upon these findings and building on our previous research on anticancer derivatives, 40–47 specifically focusing on VEGFR-2 inhibitors, 48–53 the main objective of this study was to synthesize novel derivatives of pyrazolo[3,4- d ]pyrimidine with anticancer activity, while possessing the fundamental pharmacophoric properties found in first-generation VEGFR-2 inhibitors such as sunitinib, through ring variation and bio isosteric replacement (Fig. 3).…”