Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents

Pla-López, Alberto; Castillo, Raquel; Cejudo-Marín, Rocío; García-Pedrero, Olaya; Bakir-Laso, Mariam; Falomir, Eva; Cardá, Miguel

doi:10.3390/ijms23137049

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…According to these data, compounds C.1 (carbamate), C.3 (p-fluorophenyl urea), C.12 (p-methoxyphenyl urea) and C.14 (o-methoxyphenyl urea), with no inhibitory effect towards any cell line were selected for further biological studies. 12 No effect 83 C. 13 1,9 0,8 C. 14 No effect No effect…”

Section: 21cell Proliferation Inhibitionmentioning

confidence: 99%

“…Over the last five years our research has focused on the screening of compounds able to simultaneously block biological targets of special relevance, such as VEGFR-2 and PD-L1 [12], and to study their effect on the TME [13]. For the designing of the structures we considered the results obtained in our previous studies describing the action of several sets of aryl urea derivatives U.I and U.II bearing a styryl moiety (see Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Unveiling the Potential of BenzylethyleneAryl-Urea Scaffolds for Designing of new Onco Immunomodulating Agents

Gil-Edo¹,

Royo²,

Cardá³

et al. 2023

Preprint

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Thirteen benzylethylenearyl ureas and one carbamate have been designed, synthesized and biologically evaluated as regards their antiproliferative activity on tumor cell lines HEK-293 and A-549 and on the immune and endothelial Jurkat T cells and HMEC-1, respectively. A relationship between the structure of the synthetic compounds and their antiproliferative activity has been established. Compounds C.1, C.3, C.12 and C.14 were chosen for further biological studies in order to determine their potential as oncoimmunomodulating agents. Some compounds exhibited significant inhibitory effects on both total PD-L1 and VEGFR-2 in HT-29 cell line, showing urea C.12 active against both targets. Some compounds could reduce more than 50% of cancer living cells, compared to non-treated ones, when assessed in co-cultures using HT-29 and THP-1 cells. In addition, these compounds showed no effect on the immune cell viability and significantly reduce CD11b expression, which is a promising target for immune modulation in anti-cancer therapies.

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Section: 21cell Proliferation Inhibitionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unveiling the Potential of BenzylethyleneAryl-Urea Scaffolds for Designing of new Onco Immunomodulating Agents

Gil-Edo¹,

Royo²,

Cardá³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…According to these data, compounds C.1 (carbamate), C.3 (p-fluorophenyl urea), C.12 (p-methoxyphenyl urea) and C.14 (o-methoxyphenyl urea), with no inhibitory effect toward any cell line were selected for further biological studies. 12 No effect 83 C. 13 1.9 0.8 C. 14 No effect No effect 2.2.2. Effect on Cellular PD-L1 and VEGFR-2 in Cancer Cell Lines…”

Section: Cell Proliferation Inhibitionmentioning

confidence: 99%

“…Our research group has been working on the discovery of small molecules that are able to simultaneously block some anticancer targets, such as VEGFR-2 and PD-L1 [ 12 ], and to study their effect on the TME [ 13 ]. For the design of the structures, we considered the results obtained in our previous studies that describe the action of several sets of aryl urea derivatives, U.I and U.II, bearing a styryl moiety (see Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Potential of BenzylethyleneAryl–Urea Scaffolds for the Design of New Onco Immunomodulating Agents

et al. 2023

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This work focuses on the development of thirteen benzylethylenearyl ureas and one carbamate. After the synthesis and purification of the compounds, we studied their antiproliferative action on cell lines, such as HEK-293, and cancer ones, such as HT-29, MCF-7 or A-549, on the immune Jurkat T-cells and endothelial cells HMEC-1. Compounds C.1, C.3, C.12 and C.14 were selected for further biological studies to establish their potential as immunomodulating agents. Some of the derivatives exhibited significant inhibitory effects on both targets: PD-L1 and VEGFR-2 in the HT-29 cell line, showing that urea C.12 is active against both targets. Some compounds could inhibit more than 50% of cancer cell proliferation compared to non-treated ones when assessed in co-cultures using HT-29 and THP-1 cells. In addition, they significantly reduced CD11b expression, which is a promising target for immune modulation in anticancer immunotherapies.

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“…Over the last five years, our research has focused on the screening of compounds capable of simultaneously blocking biological targets of special relevance, not only in the cancerous process but also in the maintenance of the tumor microenvironment (TME) [16].…”

Section: Introductionmentioning

confidence: 99%

Exploring BenzylethoxyAryl Urea Scaffolds for Multitarget Immunomodulation Therapies

Gil-Edo

Hernández-Ribelles²,

Royo

et al. 2023

IJMS

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Thirteen benzylethoxyaryl ureas have been synthesized and biologically evaluated as multitarget inhibitors of VEGFR-2 and PD-L1 proteins to overcome resistance phenomena offered by cancer. The antiproliferative activity of these molecules on several tumor cell lines (HT-29 and A549), on the endothelial cell line HMEC-1, on immune cells (Jurkat T) and on the non-tumor cell line HEK-293 has been determined. Selective indexes (SI) have been also determined and compounds bearing p-substituted phenyl urea unit together with a diaryl carbamate exhibited high SI values. Further studies on these selected compounds to determine their potential as small molecule immune potentiators (SMIPs) and as antitumor agents have been performed. From these studies, we have concluded that the designed ureas have good tumor antiangiogenic properties, exhibit good inhibition of CD11b expression, and regulate pathways involved in CD8 T-cell activity. These properties suggest that these compounds could be potentially useful in the development of new cancer immune treatments.

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Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents

Cited by 10 publications

References 29 publications

Unveiling the Potential of BenzylethyleneAryl-Urea Scaffolds for Designing of new Onco Immunomodulating Agents

Unveiling the Potential of BenzylethyleneAryl-Urea Scaffolds for Designing of new Onco Immunomodulating Agents

Unveiling the Potential of BenzylethyleneAryl–Urea Scaffolds for the Design of New Onco Immunomodulating Agents

Exploring BenzylethoxyAryl Urea Scaffolds for Multitarget Immunomodulation Therapies

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