Design And Synthesis Of Anti-tumor Drugs For Dopamine Receptors

According to statistics,cancer has become a serious public health problem,which seriously affects the health and the quality of people's lives,and it is one of the diseases with the highest morbidity and mortality in China.The cure of cancer has been the goal that the scientists always struggle for.However,the traditional anticancer drugs have great toxicity and side effects,and new targeted antitumor drugs are attracting more and more attention due to their excellent anti-tumor activity and low toxic side effects.Studies have shown that dopamine receptors can be expressed on the surface of many cancer cells,and the traditional dopamine D2 receptor agonist methanesulfo-nic acid bromocriptine tablets,which has been used in the clinical treatment of prolactinoma.Evidence revealed that dopamine receptors may play a role in the treatment of cancer stem cells.D2,a dopamine receptor antagonist,could inhibit leukemia stem cells,but not affect normal blood stem cells.Thus,dopamine receptors can be a class of potentially novel biomarkers of malignant tumors.A new type of compound has been designed and synthesized in this paper.The compounds we designed have both the quinazoline ring and the N-aryl piperazine structure,and these structures are separated by the long aliphatic hydrocarbons chain according to a large number of EGFR targeted antitumor drugs containing a quinazoline heterocycle structure and a large number of ligands with high affinity and capacity of dopamine receptors contain a N-aryl piperazine structure.In order to modify the structure,different groups were introduced into 6,7-position of quinazolinering as well as the nucleophilic substitution reactions taken place in the 2,3-position of quinazoline ring to combine with the structure of N-arylpiperazines.Moreover,2-4carbon atoms were selected as connecting long chains.Finally,the molecular structure of the compound was modified by changing the aryl moiety in the N-aryl piperazine moiety.In this paper,34 different structural compounds were synthesized and divided into two different kinds,2-substituted quinazoline and 4-substituted quinazoline derivatives.The synthesis reaction conditions were optimized by adjusting different parameters and the bioactivity of the compounds was tested with the Peking University Health Science Center.Due to the limitation of time,only the IC50 values of some compounds for human non-small cell lung cancer A549 cell lines were shown in this context.All test compounds showed in vitro inhibitory activity against A549 cell lines in which IC50 of compound 1c was 2.206 ?M.Projects that are currently being tested at the same time include but are not limited to the following: in vitro tests for human pancreatic cancer cell lines;in vitro inhibition of breast cancer stem cell stem cells;mouse-induced lung cancer models,inoculation of human breast cancer cells in vitro,Breast cancer model,pancreatic cancer model mice;for dopamine receptor D1-D5 five types of receptor subtype affinity and selectivity test.