The convergent total syntheses of three 14membered macrolide natural products, mutolide, nigrosporolide and (4S,7S,13S)-4,7-dihydroxy-13-tetradeca-2,5,8-trienolide have been achieved. The key synthetic features include Shiina macrolactonization to assemble the 14-membered macrocyclic core, Wittig or Still-Gennari olefination and selective reduction of propargylic alcohol to construct the Eor Z-olefins. Cross metathesis was also highlighted as an efficient tool to forge the formation of E-olefin. The three synthetic macrolides were evaluated for their cytotoxic activity against three human cancer cell lines as well as for inhibitory effect on CFTR-mediated chloride secretion in human intestinal epithelial (T84) cells. Mutolide displayed significant cytotoxic activity against HCT116 colon cancer cells with an IC 50 of ~12 μM as well as a potent CTFR inhibitory effect with an IC 50 value of ~1 μM.

Background: Resistance to chemotherapeutic agents is usually found in cancer stem cells (CSCs) and cancer stem-like cells that are often regarded as the target for cancer monitoring. However, the different patterns of their transcriptomic profiling is still unclear. Objective: This study aims to illustrate the transcriptomic profile of CSCs and butyrate-resistant colorectal carcinoma cells (BR-CRCs), by comparing them with parental colorectal cancer (CRC) cells in order to identify distinguishing transcription patterns of the CSCs and BR-CRCs. Methods: Parental CRC cells HCT116 (HCT116-PT) were cultured and induced to establish the butyrate resistant cell model (HCT116-BR). Commercial enriching of the HCT116-CSCs were grown in a tumorsphere suspension culture, which was followed firstly by the assessment of butyrate tolerance using MTT and PrestoBlue. Then their gene expression profiling was analyzed by microarray. Results: The results showed that both butyrate-resistant HCT116 cells (HCT116-BR) and HCT116-CSCs were more tolerant a butyrate effects than HCT116-PT cells. Differentially expressed gene profiles exhibited that IFI27 , FOXQ1 , PRF1 , and SLC2A3 genes were increasingly expressed in CSCs, and were dramatically overexpressed in HCT116-BR cells when compared with HCT116-PT cells. Moreover, PKIB and LOC399959 were downregulated both in HCT116-CSCs and HCT116-BR cells. Conclusion: Our findings shed light on the transcriptomic profiles of chemoresistant CRC cells. This data should be useful for further study to provide guidelines for clinical prognosis to determine the guidelines for CRC treatment, especially in patients with chemoresistance and designing novel anti-neoplastic agents.

A neurodegenerative disorder is a condition that causes a degeneration of neurons in the central nervous system, leading to cognitive impairment and movement disorders. An accumulation of oxidative stress in neurons contributes to the pathogenesis of neurodegenerative disorders. Over the past few years, several studies have suggested that short-chain fatty acids, metabolites of the gut microbiota, might have a beneficial effect in neurodegenerative disorders. A G protein-coupled receptor 43