Generic placeholder image

当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

新型长春花生物碱4-氯喹啉和4-氯噻吩的生物活性

卷 19, 期 3, 2019

页: [222 - 230] 页: 9

弟呕挨: 10.2174/1568009618666180430142233

价格: $65

摘要

背景:长春花生物碱是属于抗有丝分裂剂类的重要抗癌药物。最常用的物质是长春碱和长春新碱,其他化合物是长春瑞滨和长春氟宁。它们都是非常有效的药物,但它们的使用受到严重副作用的限制,包括神经毒性和骨髓抑制。因此,开发具有相似功效但毒性较低的新型长春花生物碱是非常重要的。 方法:在这里,我们分析了两种新化合物,即4-氯喹啉和4-氯噻嗪,它们的生物活性。将这些新化合物以临床相关浓度应用于白血病细胞系。为了比较,还测试了已建立的长春花生物碱长春碱,长春新碱,长春瑞滨和长春氟宁。 结果:两种新物质均可降低细胞增殖。使用反映早期和晚期细胞凋亡的两种不同方法发现细胞凋亡增加。细胞周期分析显示G1细胞明显减少,G2 / M细胞增加,表明有丝分裂停滞。通常,4-氯卡拉平和4-氯噻嗪在浓度高于长春碱,长春新碱和长春瑞滨所需的浓度下引起这些作用,但效力大约在长春氟宁的范围内。 结论:总之,结果表明这些新的长春花生物碱可能是有效的,并值得进一步分析。

关键词: 细胞毒性,HL-60细胞,长春花生物碱,氯磷酰胺,氯噻嗪,长春碱,长春新碱,长春氟宁,长春瑞滨。

[1]
Moudi M, Go R, Yien CY, Nazre M. Vinca alkaloids. Int J Prev Med 2013; 4(11): 1231-5.
[2]
Noble RL, Beer CT, Cutts JH. Role of chance observations in chemotherapy: Vinca rosea. Ann N Y Acad Sci 1958; 76(3): 882-94.
[3]
Lee JC, Harrison D, Timasheff SN. Interaction of vinblastine with calf brain microtubule protein. J Boil Chem 1975; 250(24): 9276-82.
[4]
Gigant B, Wang C, Ravelli RB, et al. Structural basis for the regulation of tubulin by vinblastine. Nature 2005; 435(7041): 519-22.
[5]
Cragg GM. Anticancer Agents from Natural Products. 2nd ed. Boca Raton: CRC Press 2012; p. 767.
[6]
Caron JM, Herwood M. Vinblastine, a chemotherapeutic drug, inhibits palmitoylation of tubulin in human leukemic lymphocytes. Chemotherapy 2007; 53(1): 51-8.
[7]
DeVita VT. DeVita, Hellman, and Rosenberg’s cancer principles & practice of oncology. 2008.
[8]
Binet S, Chaineau E, Fellous A, et al. Immunofluorescence study of the action of navelbine, vincristine and vinblastine on mitotic and axonal microtubules. Int J Cancer 1990; 46(2): 262-6.
[9]
Hill SA, Lonergan SJ, Denekamp J, Chaplin DJ. Vinca alkaloids: anti-vascular effects in a murine tumour. Eur J Cancer 1993; 29A(9): 1320-4.
[10]
Himes RH, Kersey RN, Heller-Bettinger I, Samson FE. Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on microtubules in vitro. Cancer Res 1976; 36(10): 3798-802.
[11]
Zingirian M, Carbone A. Paracentral and central circular static campimetry on a tangential graph. Ann Ottalmol Clin Ocul 1963; 89: 116-25.
[12]
Scalone S, Sorio R, Bortolussi R, Lombardi D, La Mura N, Veronesi A. Vinorelbine-induced acute reversible peripheral neuropathy in a patient with ovarian carcinoma pretreated with carboplatin and paclitaxel. Acta Oncol 2004; 43(2): 209-11.
[13]
Ngo QA. Nguyen le, A.; Vo, N.B.; Nguyen, T.H.; Roussi, F.; Nguyen, T.H.; Nguyen, V.T. Synthesis and antiproliferativeactivity of new vinca alkaloids containing an alpha,beta-unsaturated aromatic side chain. Bioorg Med Chem Lett 2015; 25(23): 5597-600.
[14]
Collins SJ, Ruscetti FW, Gallagher RE, Gallo RC. Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proc Natl Acad Sci USA 1978; 75(5): 2458-62.
[15]
Mohamed EY, Sami W, Alotaibi A, Alfarag A, Almutairi A, Alanzi F. Patients’ satisfaction with primary health care centers’ services, Majmaah, Kingdom of Saudi of Saudi Arabia. Int J Health Sci (Qassim) 2015; 9(2): 163-70.
[16]
Gidding CE, Kellie SJ, Kamps WA, de Graaf SS. Vincristine revisited. Crit Rev Oncol Hematol 1999; 29(3): 267-87.
[17]
Detrich HW III, Parker SK, Williams RC Jr, Nogales E, Downing KH. Cold adaptation of microtubule assembly and dynamics. Structural interpretation of primary sequence changes present in the alpha- and beta-tubulins of Antarctic fishes. J Boil Chem 2000; 275(47): 37038-47.
[18]
Ngo QA, Nguyen LA, Vo NB, et al. Synthesis and antiproliferativeactivity of new vinca alkaloids containing an α,β-unsaturated aromatic side chain. Bioorg Med Chem Lett 2015; 25(23): 5597-600.
[19]
Tang DG, Li L, Zhu Z, Joshi B. Apoptosis in the absence of cytochrome c accumulation in the cytosol. Biochem Biophys Res Commun 1998; 242(2): 380-4.
[20]
Landini I, Bartolozzi B, Banchelli I, Degli Innocenti A, Nocentini O, Bernabei PA. In vitro activity of vinorelbine on human leukemia cells. J Chemother 2001; 13(3): 309-15.
[21]
Thomadaki H, Floros KV, Scorilas A. Molecular response of HL-60 cells to mitotic inhibitors vincristine and taxol visualized with apoptosis-related gene expressions, including the new member BCL2L12. Ann N Y Acad Sci 2009; 1171: 276-83.
[22]
Jean-Decoster C, Brichese L, Barret JM, et al. Vinflunine, a new vinca alkaloid: cytotoxicity, cellular accumulation and action on the interphasic and mitotic microtubule cytoskeleton of PtK2 cells. Anticancer Drugs 1999; 10(6): 537-43.
[23]
Bonfil RD, Russo DM, Binda MM, Delgado FM, Vincenti M. Higher antitumor activity of vinflunine than vinorelbine against an orthotopic murine model of transitional cell carcinoma of the bladder. Urol Oncol 2002; 7(4): 159-66.
[24]
Zucker RM, Whittington K, Price BJ. Differentiation of HL-60 cells: cell volume and cell cycle changes. Cytometry 1983; 3(6): 414-8.
[25]
Kolomeichuk SN, Terrano DT, Lyle CS, Sabapathy K, Chambers TC. Distinct signaling pathways of microtubule inhibitors--vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively. FEBS J 2008; 275(8): 1889-99.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy