Abstract
In this work, we report 14 novel quinazoline derivatives as immune checkpoint inhibitors, IDO1 and PD-L1. The antitumor screening of synthesized compounds on ovarian cancer cells indicated that compound V-d and V-l showed the most activity with IC50 values of about 5 μM. Intriguingly, compound V-d emerges as a stand out, triggering cell death through caspase-dependent and caspase-independent manners. More importantly, V-d presents its ability to hinder tumor sphere formation and re-sensitized cisplatin-resistant A2780 cells to cisplatin treatment. These findings suggest that compound V-d emerges as a promising lead candidate for the future development of immuno anticancer agents.
Keywords:
Immune check point; Indoleamine 2,3-dioxygenase 1; Ovarian cancer; Quinazoline.
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MeSH terms
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Antineoplastic Agents* / chemical synthesis
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Antineoplastic Agents* / chemistry
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Antineoplastic Agents* / pharmacology
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B7-H1 Antigen / antagonists & inhibitors
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B7-H1 Antigen / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Design*
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Drug Screening Assays, Antitumor*
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Humans
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Immune Checkpoint Inhibitors* / chemical synthesis
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Immune Checkpoint Inhibitors* / chemistry
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Immune Checkpoint Inhibitors* / pharmacology
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Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
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Molecular Structure
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Quinazolines* / chemical synthesis
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Quinazolines* / chemistry
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Quinazolines* / pharmacology
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Structure-Activity Relationship
Substances
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Quinazolines
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Immune Checkpoint Inhibitors
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Antineoplastic Agents
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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B7-H1 Antigen
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CD274 protein, human
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IDO1 protein, human