Design of anticancer agents utilizing streptozocin for in silico optimization of properties and pattern recognition identification of group features.

Q2 Pharmacology, Toxicology and Pharmaceutics
Ronald Bartzatt
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Abstract

Streptozocin has been shown to be useful in the clinical treatment of malignant neuroendocrine tumors of the pancreas. The poor prognosis for patients having malignant tumors of pancreas suggests the investigation and development of new therapeutics. Nine analogs to streptozocin are determined by in silico physicochemical analysis and generation of structures by modeling from functional group isosteres. In these analogs is preserved the alkylating nitrosourea moiety, however, the covalently bonded substituent has significant hydrogen bonding sites and may include a ring structure. Analogs retain a broad range in lipophilicity, having a range of Log P from -2.798 (hydrophilic) to 3.001 (lipophilic). Standard deviation of molecular masses is only 12.6% of the group mean, so a small alteration in size occurs which is also reflected by only a 15.5% deviation in molecular volumes. Streptozocin and seven analogs show zero violations of the Rule of 5 which suggests favorable bioavailability. All compounds showed at least seven hydrogen bond acceptors with a strong positive correlation between hydrophilicity to the total number of hydrogen bond acceptors and donors. Analysis of similarity (ANOSIM) and discriminant analysis determined that streptozocin is highly similar to all nine analogs. However hierarchical cluster analysis and K-means cluster analysis were able to elucidate patterns of associations and differentiation among the ten compounds. This study demonstrates the efficacy of utilizing in silico optimization and pattern recognition to elucidate potential anticancer drugs.

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利用链脲佐菌素设计抗癌药物的性能优化和模式识别识别的群体特征。
链脲佐菌素已被证明是有用的临床治疗恶性神经内分泌肿瘤的胰腺。胰腺恶性肿瘤患者预后不良,提示研究和开发新的治疗方法。通过计算机物理化学分析和从官能团同分异构体模型生成的结构,确定了9个链脲佐菌素类似物。在这些类似物中保留烷基化亚硝基脲部分,然而,共价键取代基具有显著的氢键位点,并且可能包括环结构。类似物的亲脂性范围很广,其logp范围从-2.798(亲水)到3.001(亲脂)。分子质量的标准差仅为群体平均值的12.6%,因此分子大小的变化很小,这也反映在分子体积的偏差仅为15.5%。链脲佐菌素和7个类似物显示零违反规则5,这表明良好的生物利用度。所有化合物均含有至少7个氢键受体,且亲水性与氢键受体和给体总数呈正相关。相似度分析(ANOSIM)和判别分析确定链脲佐菌素与所有9种类似物高度相似。然而,层次聚类分析和k -均值聚类分析能够阐明10种化合物之间的关联和分化模式。本研究证明了利用芯片优化和模式识别来阐明潜在抗癌药物的有效性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Open Medicinal Chemistry Journal
Open Medicinal Chemistry Journal Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
4.40
自引率
0.00%
发文量
4
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