Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized.

The first and asymmetric total synthesis of cyclocitrinol, an unusual C25 steroid, has been accomplished in a linear sequence of 18 steps from commercially available compound 11. The synthetically challenging bicyclo[4.4.1] A/B ring system with a strained bridgehead (anti-Bredt) double bond of cyclocitrinol was constructed efficiently and diastereoselectively via a type II intramolecular [5 + 2] cycloaddition.

BackgroundWe aimed to examine the expression of miR-1307 in chemosensitive and chemoresistant epithelial ovarian cancer tissues and cell lines and to analyze the clinicopathological significance of miR-1307 in ovarian cancer.MethodsMicroRNA microarray was used to screen differentially expressed microRNAs between the chemosensitive and chemoresistant epithelial ovarian cancer tissues. RT-PCR was used to validate the candidate microRNA. The potential target genes and their enriched biological pathways of microRNA were also analyzed. Dual Luciferase Reporter Gene Assay was conducted to validate the regulation of miRNA-1307 on the 3’-UTR of DAPK3.ResultsmiRNA-1307 was up-regulated in the chemoresistant epithelial ovarian cancer tissues compared to the chemosensitive counterparts. The up-regulation of miRNA-1307 was not associated with menopause, tumor differentiation state, clinical stage, and lymph node metastasis of ovarian cancer. Gene ontology analysis of miR-1307 candidate target genes indicated that miR-1307 candidate target genes were enriched in the processes of cell proliferation and differentiation, nucleotide synthesis and metabolism, and lymphocytes activation.ConclusionOur results suggest that miRNA-1307 may play a role in the development of chemoresistance in ovarian cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0143-5) contains supplementary material, which is available to authorized users.

The observation of an unexpected oxidative rearrangement coupling reaction led to the development of a novel method for the efficient functionalization of tetrahydro-β-carbolines (THβCs). The treatment of THβCs with photogenerated singlet oxygen ( O ) afforded unstable dioxetanes, which underwent further transformation to form new bonds in the presence of trifluoroacetic acid. This operationally simple protocol exhibits broad functional-group tolerance and is suitable for the late-stage functionalization of complex druglike molecules.

The first asymmetric total synthesis of the highly strained compound cerorubenic acid-III is reported. A type II intramolecular [5 + 2] cycloaddition allowed efficient and diastereoselective construction of the synthetically challenging bicyclo[4.4.1] ring system with a strained bridgehead (anti-Bredt) double bond in the final product. A unique transannular cyclization installed the vinylcyclopropane moiety with retention of the desired stereochemistry.

Natural products with a bridgehead double bond, such as taxol and CP molecules, have long attracted considerable attention from chemists because of their promising bioactivity and structural complexity, with the high ring-strain energy in the ring systems representing a formidable synthetic challenge. Herein, strategies for the total synthesis of such complex natural products are reviewed for the first time by using 26 representative studies. Methods for constructing the bridged ring system and bridgehead double bond have been emphasized, including syntheses of the same natural product by different research groups using different strategies, to showcase the diversity of thought and creativity in this area. The total synthesis of these natural products not only provides precious bioactive substances and promising candidates for drug discovery but also has stimulated incredible advances in the development of new strategies and synthetic methods.

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As commented by the Nobelist James Black that "The most fruitful basis of the discovery of a new drug is to start with an old drug", drug repurposing represents an attractive drug discovery strategy. Despite the success of several repurposed drugs on the market, the ultimate therapeutic potential of a large number of non-cancer drugs is hindered during their repositioning due to various issues including the limited efficacy and intellectual property. With the increasing knowledge about the pharmacological properties and newly identified targets, the scaffolds of the old drugs emerge as a great treasure-trove towards new cancer drug discovery. In this review, we summarize the recent advances in the development of novel small molecules for cancer therapy by scaffold repurposing with highlighted examples. The relevant strategies, advantages, challenges and future research directions associated with this approach are also discussed.