吲哚[2,3-a]吡咯[3,4-c]咔唑n -糖苷类新衍生物的Antiproliferative活性

Q3 Pharmacology, Toxicology and Pharmaceutics
Marina P. Kiseleva, L. Borisova, G. Smirnova, Yu. A. Borisova, A. Lantsova, E. Sanarova, L. Nikolaeva, Lydia V. Ektova, M. V. Komarova
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引用次数: 2

摘要

引言:高效原创抗癌药物的研制仍然是肿瘤治疗科学研究的迫切方向。在这方面有希望的团体之一是吲哚类 以及它们的衍生物,它们能够启动肿瘤细胞死亡的各种途径。本研究的目的是评估一种新的N-糖苷取代的俄罗斯衍生物的抗增殖活性吲哚卡巴唑 6-氨基-12-(α-L-阿拉伯吡喃酰基)吲哚并[2,3-a]吡咯并[3,4-c]咔唑-5,7-二酮(LCS-1208)在小鼠可移植肿瘤模型和Balb/c裸鼠中的人类肿瘤上的作用。材料和方法:吲哚卡巴唑 在小鼠的可移植肿瘤——淋巴白血病L-1210、宫颈癌(CC-5)和结肠腺癌(CAC)——上,通过50、75、100mg/kg单剂量的5倍腹膜内给药(ip)LCS-1208物质来评估对LCS-1208的敏感性。通过静脉内给药对人结肠癌癌症SW620的皮下异种移植物进行LCS-1208lyo剂型的有效性的研究(iv)。通过与对照动物相比,治疗动物的肿瘤生长抑制(TGI)和寿命延长(ILS)来评估抗肿瘤效果。根据肿瘤/对照(T/C%)标准(最大标准T/C≤42%)对异种移植物的特异性抗肿瘤活性进行评估。结果和讨论:根据研究结果,在总剂量375 mg/kg的ip给药情况下,对LCS-1208物质的作用最敏感的是CAC,TGI=97–62%,治疗后16天p≤0.001,ILS=36%(TGI≥70%和ILS≥25%的标准)。在人类癌症SW620的异种移植物上,在静脉注射至Balb/c裸鼠的情况下,LCS-1208 lyo药物剂型在50至150 mg/kg的总剂量范围内的有效性设定为T/c=35–2%(标准T/c<42%)。结论:本研究结果提示LCS-1208治疗人类结肠恶性肿瘤可能有效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antiproliferative activity of a new derivative from the class of N-glycoside of indolo[2,3-a]pyrrolo[3,4-c]carbazoles
Introduction: The creation of highly effective original anticancer drugs remains an urgent direction of scientific research in tumor therapy. One of the promising groups in this regard is indolocarbazoles and their derivatives, which are capable of initiating various pathways of tumor cell death. The aim of the study was to evaluate an antiproliferative activity of a new, Russian derivative of N-glycoside substituted indolocarbazole 6-amino-12-(α-L-arabinopyranosyl)indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7-dione (LCS-1208) on models of transplantable tumors of mice and on human tumors in Balb/c nude mice. Materials and methods: Indolocarbazole sensitivity to LCS-1208 was assessed on transplantable tumors of mice – lymphatic leukemia L-1210, cervical carcinoma (CC-5), and colon adenocarcinoma (CAC) by five-fold intraperitoneal administration (ip) of the LCS-1208 substance in single doses of 50, 75, 100 mg/kg. Investigation into the effectiveness of the LCS-1208 lyo dosage form was performed on subcutaneous xenografts of human colon cancer SW620 by an intravenous administration (iv). The antitumor effect was evaluated by the tumor growth inhibition (TGI) and an increase in life span (ILS) of the treated animals as compared with the control ones. Evaluation of specific antitumor activity on xenografts was performed according to the tumor/control (T/C%) criterion (maximum criterion T/C≤42%). Results and discussion: According to the results of the study, the most sensitive to the action of the LCS-1208 substance in the case of an ip administration of a total dose of 375 mg/kg were CAC with TGI=97–62%, p≤0.001 up to 16 days after the treatment, and ILS=36% (criteria for TGI≥70% and ILS≥25%). On xenografts of a human colon cancer SW620, the effectiveness of the LCS-1208 lyo drug dosage form within the range of total doses from 50 to 150 mg/kg in case of iv to Balb/c nude mice was set at T/C = 35–2% (criterion T/C<42%). Conclusion: The presented results suggest possible effectiveness of LCS-1208 in treatment of colon malignant tumors of humans.
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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