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Naphthyl quinoxaline thymidine conjugate is a potent anticancer agent post UVA activation and elicits marked inhibition of tumor growth through vaccination.

Abstract：

:Anticancer anthracyclines are cytotoxic drugs that can induce antitumor immune response as a secondary effect through immunogenic cell death (ICD) mechanism. However, the immunogenic potency is quite limited, possibly due to that these chemotherapeutic agents are not specifically developed as ICD inducers. Thus, new drug entities through studies focusing on enhanced ICD induction would significantly promote antitumor immune response in the vaccination application. We report here a naphthyl quinoxaline thymidine conjugate as a new class of cytotoxic compounds that effectively induced in vivo antitumor activity through the vaccination application. Synthesized naphthyl quinoxaline conjugates were weak fluorescent thymidine analog yet exhibited a pronounced anticancer activity in the low nanomolar range post UVA activation. The potent activity of naphthyl conjugate was able to induce the marked detection of ICD markers including ATP and HMGB1 extracellular and calreticulin intracellularly at 2 h post UVA activation. Most importantly, mice vaccinated with cells treated with naphthyl conjugate plus UVA exhibited complete tumor growth inhibition in the tumor challenge study, and the induced immunogenic inhibition was much more effective than that of mitoxantrone anthracycline drug. All these results demonstrate the high potential of naphthyl quinoxaline conjugate for the cancer cell vaccine against tumor.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Yuan Y,Wang Z,Yang R,Qian T,Zhou Q

doi

10.1016/j.ejmech.2019.03.051

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

255-264

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(19)30275-2

journal_volume

171

pub_type

杂志文章

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