阅读说明：本技术 多杂环-吡唑啉类衍生物在制备抗非小细胞肺癌药物中的应用 (Application of polyheterocycle-pyrazoline derivatives in preparation of non-small cell lung cancer resistant drugs ) 是由 林兆民 高冬芳 张璐 张明 陈元 王鹏 林御星 于 2020-05-27 设计创作，主要内容包括：本发明公开了一种化合物2-(5-(苯并[d][1,3]二氧杂-5-基)-3-苯基-4,5-二氢-1H-吡唑-1-基)-4-(吡啶-4-基)噻唑(简略记为BPT)在制备抗非小细胞肺癌药物中的应用。实验证实本发明提供的化合物BPT能够显著抑制A549细胞生长,并且抑制作用优于临床药物5-FU。BPT有望作为一种有效的抑制肿瘤生长工具,为开发非小细胞肺癌治疗药物奠定基础。(The invention discloses application of a compound 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole (abbreviated as BPT) in preparation of a non-small cell lung cancer resistant medicament. Experiments prove that the compound BPT provided by the invention can obviously inhibit the growth of A549 cells, and the inhibition effect is superior to that of a clinical drug 5-FU. The BPT is expected to be an effective tool for inhibiting tumor growth and lays a foundation for developing non-small cell lung cancer treatment medicines.)

1. the use of the compound 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridin-4-yl) thiazole, wherein the 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridin-4-yl) thiazole is abbreviated as BPT and has the formula shown in formula (I):

Technical Field

The invention relates to application of a polyheterocycle-pyrazoline derivative in preparing a lung cancer resistant medicament, in particular to application of a fluorescent compound 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole (abbreviated as BPT) in preparing a non-small cell lung cancer resistant medicament for inhibiting the growth of A549 cancer cells.

Background

Tumors are one of the well-known diseases that seriously endanger human health, and the morbidity and mortality rate rise year by year. It is expected that 2140 new cases of diagnosed tumors will occur worldwide in 2030, and the tumor death will reach 1320 thousands. Lung cancer is a global problem in cancer treatment because of its late discovery and high lethality rate. Environmental factors such as air pollution and bad living habits such as smoking also aggravate the development of lung cancer. In lung cancer cases, non-small cell lung cancer accounts for about 85% of the total lung cancer, and about 75% of patients are found to be in the middle and advanced stages, with very low 5-year survival rates. Chemotherapy plays an important role in various therapeutic approaches to lung cancer. The small molecular compound can be used as a tumor inhibiting factor and becomes a promising new treatment strategy.

However, a very big challenge faced by lung cancer chemotherapy in clinic is poor drug selectivity, i.e. when tumor is treated, toxic and side effects are caused to normal tissues, so that treatment fails, and the drug with poor selectivity can easily cause drug resistance of tumor cells. Therefore, there is an urgent need to develop more compounds or agents that inhibit the growth of lung cancer cells. Through search, the application of the fluorescent compound 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole in the preparation of the anti-lung cancer medicament for inhibiting the growth of A549 cancer cells is not reported.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide the application of a compound 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole (abbreviated as BPT) in preparing a non-small cell lung cancer resistant medicament for inhibiting the growth of A549 cancer cells.

The invention relates to application of 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole serving as a compound in preparation of medicines for resisting non-small cell lung cancer, wherein the 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole is abbreviated as BPT, and the structural formula of the BPT is shown as a formula (I):

in the above application: the dosage of the 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole capable of effectively inhibiting the growth of A549 cells is 1-5 mu M.

The cell biology experiment and the result of the compound 2- (5- (benzo [ d ] [1,3] dioxa-5-yl) -3-phenyl-4, 5-dihydro-1H-pyrazol-1-yl) -4- (pyridine-4-yl) thiazole inhibiting the growth of A549 carcinoma are as follows:

1. effect of compound BPT on a549 cell survival.

Experimental groups: BPT at concentrations of 0.1. mu.M, 1. mu.M, 5. mu.M, 10. mu.M was treated with A549 cells for 24h and 48h, respectively. Negative control: DMSO (0.02%, v/v), positive control: the clinical anticancer drug, namely, the pentafluorouracil (5-FU).

The results show that: the survival of a549 cells was significantly inhibited after 24h and 48h of treatment of a549 cells with 1 μ M, 5 μ M, 10 μ M BPT, see fig. 1. The specific action results are shown in the following table:

2. effect of compound BPT on a549 cell morphology.

Experimental groups: cell morphology changes were photographed 12h,24h and 48h after treatment of A549 cells with BPT at concentrations of 0.1. mu.M, 1. mu.M, 5. mu.M, 10. mu.M, respectively. Control group: DMSO (0.02%, v/v).

The results show that: under the above time conditions, treatment with 5. mu.M, 10. mu.M BPT reduced the number of A549 cells, as shown in FIG. 2.

3. The compound BPT has better inhibition effect on A549 cells than the clinical drug 5-FU.

Experimental groups: half of 48h of compound BPT and 5-FU treated A549 cells were calculatedInhibitory Concentration (IC)₅₀). IC for finding BPT₅₀The value is 2.6. mu.M, which is superior to the clinical drug 5-FU (9.4. mu.M).

Statistical treatment of the above experimental data:

experimental data are expressed as mean ± standard error, as determined by t-test: p <0.05 indicates significant differences; p <0.01 indicates a very significant difference.

From the above experiments and the results thereof, the following conclusions can be drawn:

BPT can obviously inhibit the growth of A549 cells, and the inhibition effect is better than that of a clinical drug 5-FU.

The result of the BPT shown in the invention for inhibiting the growth of A549 carcinoma cells indicates that the BPT is expected to be an effective tumor growth inhibition tool, and lays a foundation for developing anti-non-small cell lung cancer treatment medicines.

Drawings

FIG. 1: BPT inhibits a549 cell survival.

Wherein: a, after BPT treatment of A549 cells for 24 hours, the survival rate of the A549 cells is detected.

And B, detecting the survival rate of the A549 cells 48h after the A549 cells are treated by the BPT.

FIG. 2: BPT promotes a549 morphology change and reduces cell number.

After the A549 cells are treated by BPT at different concentrations for 12h,24h and 48h, the morphology and the quantity change of the A549 cells are observed by microscopic pictures.

Detailed Description

The present invention will be described in detail with reference to the following detailed drawings and examples. The following examples are only preferred embodiments of the present invention, and it should be noted that the following descriptions are only for explaining the present invention and not for limiting the present invention in any form, and any simple modifications, equivalent changes and modifications made to the embodiments according to the technical spirit of the present invention are within the scope of the technical solution of the present invention.

In the following examples, materials, cells, reagents and the like used were obtained commercially unless otherwise specified.