目的总结Top1抑制剂与Tdp1抑制剂整体概况,探究其发展趋势,为后续研究提供参考。方法运用CiteSpace 5.7.R5软件对2012年1月—2022年4月收录在Web of Science(WOS)核心合集数据库中Top1抑制剂与Tdp1抑制剂的相关文献进行作者、机构、被...目的总结Top1抑制剂与Tdp1抑制剂整体概况,探究其发展趋势,为后续研究提供参考。方法运用CiteSpace 5.7.R5软件对2012年1月—2022年4月收录在Web of Science(WOS)核心合集数据库中Top1抑制剂与Tdp1抑制剂的相关文献进行作者、机构、被引期刊、国家、关键词可视化分析。结果共纳入有效文献1186篇,Yves Pommier为发文量最高的作者;美国国家癌症研究所为发文量最高的机构,机构之间具有一定的联系但是合作较为分散,美国研究该领域最全面;Journal of Biological Chemistry为被引率最高的期刊;关键词细胞凋亡、抗肿瘤、抑制剂出现频率高,Top1抑制剂与Tdp1抑制剂研究方向集中于Top1抑制剂、Tdp1抑制剂的发现、合成以及抗肿瘤机制。结论开发更多新型Top1抑制剂、Tdp1抑制剂甚至Top1-Tdp1双靶点抑制剂以进一步提高药物抗肿瘤活性将成为未来研究趋势。展开更多
Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was car...Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, Cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.展开更多
Oripavine is the major alkaloid of Papaver orientale. It is an important intermediate in the biosynthesis of morphine alkaloids. Recently, new Papaver somniferum strains have been developed which accumulate thebaine a...Oripavine is the major alkaloid of Papaver orientale. It is an important intermediate in the biosynthesis of morphine alkaloids. Recently, new Papaver somniferum strains have been developed which accumulate thebaine and oripavine, but not morphine and codeine. Therefore, the chemistry of oripavine has been studied intensively to synthesize opioid pharmaceuticals such as oxymorphone, naloxone and buprenorphine.展开更多
R-loop structures （RNA：DNA hybrids） have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 （TOP1）, an essen...R-loop structures （RNA：DNA hybrids） have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 （TOP1）, an essential manipulator of DNA topology during RNA transcription and DNA replication processes, can prevent R-loop accumulation by removing the positive and negative DNA supercoiling that is made by RNA polymerases during transcription. TOP1 is required for plant development, but little is known about its function in preventing co-transcriptional R-loop accumulation in various biological processes in plants. Here we show that knockdown of OsTOP1 strongly affects rice development, causing defects in root archi- tecture and gravitropism, which are the consequences of misregulation of auxin signaling and transporter genes. We found that R-loops are naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1 is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets the accurate expression levels of auxin-related genes by preventing the overaccumulation of inherent R-loops. Our data reveal R-loops as important factors in polar auxin transport and plant root development, and highlight that OsTOP1 functions as a key to link transcriptional R-loops with plant hormone signaling, provide new in- sights into transcriptional regulation of hormone signaling in plants.展开更多
文摘目的总结Top1抑制剂与Tdp1抑制剂整体概况,探究其发展趋势,为后续研究提供参考。方法运用CiteSpace 5.7.R5软件对2012年1月—2022年4月收录在Web of Science(WOS)核心合集数据库中Top1抑制剂与Tdp1抑制剂的相关文献进行作者、机构、被引期刊、国家、关键词可视化分析。结果共纳入有效文献1186篇,Yves Pommier为发文量最高的作者;美国国家癌症研究所为发文量最高的机构,机构之间具有一定的联系但是合作较为分散,美国研究该领域最全面;Journal of Biological Chemistry为被引率最高的期刊;关键词细胞凋亡、抗肿瘤、抑制剂出现频率高,Top1抑制剂与Tdp1抑制剂研究方向集中于Top1抑制剂、Tdp1抑制剂的发现、合成以及抗肿瘤机制。结论开发更多新型Top1抑制剂、Tdp1抑制剂甚至Top1-Tdp1双靶点抑制剂以进一步提高药物抗肿瘤活性将成为未来研究趋势。
文摘Over the past years natural products and/or their derivatives have continued to provide cancer chemotherapeutics. Glycosides derivatives of emodin are known to possess anticancer activities. An in silico study was carried out to evaluate emodin derivatives as inhibitors of Arylamine N-Acetyltransferase 2, Cyclooxygenase 2 and Topoisomerase 1 enzymes, predict their pharmacokinetics and explore their bonding modes. Molecular docking study suggested that D2, D5, D6 and D9 to be potent inhibitors of NAT2, while D8 was suggested to be a potent inhibitor of TOP1. Derivatives D2, D5, D6 and D9 bind to the same pocket with different binding conformation. Pharmacokinetic study suggested that selected emodin derivatives can be potential cancer chemotherapeutic agent. Physicochemical parameters such density, balaban index, surface tension, logP and molar reflectance correlated to compounds activity. These finding provides a potential strategy towards developing NAT2 and TOP1 inhibitors.
文摘Oripavine is the major alkaloid of Papaver orientale. It is an important intermediate in the biosynthesis of morphine alkaloids. Recently, new Papaver somniferum strains have been developed which accumulate thebaine and oripavine, but not morphine and codeine. Therefore, the chemistry of oripavine has been studied intensively to synthesize opioid pharmaceuticals such as oxymorphone, naloxone and buprenorphine.
基金This work was supported by the National Natural Science Foundation of China （30900070, to C.C.）, Tsinghua University initiative Scientific Research Program, Tsinghua-Peking Joint Center for Life Sciences, and 1000 Young Talent Program of China （to The Sun Lab）. S.S. and E.W. were supported by postdoctoral fellowships from Tsinghua-Peking Joint Center for Life Sciences.
文摘R-loop structures （RNA：DNA hybrids） have important functions in many biological processes, including transcriptional regulation and genome instability among diverse organisms. DNA topoisomerase 1 （TOP1）, an essential manipulator of DNA topology during RNA transcription and DNA replication processes, can prevent R-loop accumulation by removing the positive and negative DNA supercoiling that is made by RNA polymerases during transcription. TOP1 is required for plant development, but little is known about its function in preventing co-transcriptional R-loop accumulation in various biological processes in plants. Here we show that knockdown of OsTOP1 strongly affects rice development, causing defects in root archi- tecture and gravitropism, which are the consequences of misregulation of auxin signaling and transporter genes. We found that R-loops are naturally formed at rice auxin-related gene loci, and overaccumulate when OsTOP1 is knocked down or OsTOP1 protein activity is inhibited. OsTOP1 therefore sets the accurate expression levels of auxin-related genes by preventing the overaccumulation of inherent R-loops. Our data reveal R-loops as important factors in polar auxin transport and plant root development, and highlight that OsTOP1 functions as a key to link transcriptional R-loops with plant hormone signaling, provide new in- sights into transcriptional regulation of hormone signaling in plants.
