A versatile strategy for convenient circular bivalent functional nucleic acids construction.

Functional nucleic acids (FNAs), such as aptamers, nucleic acid enzymes and riboswitches play essential roles in various fields of life sciences. Tailoring of ingenious chemical moieties toward FNAs can enhance their biomedical properties and/or confer them with exogenic biological functions that, in turn, can considerably expand their biomedical applications, or even improve their clinical translations. Herein, we report the first example of a general chemical tailoring strategy that enables the divergent ligation of DNA sequences. By applying this technology, different types of aptamers and single-stranded nucleic acids of various lengths could be efficiently tailored to deliver the designed circular bivalent aptamers (CBApts) and cyclized DNA sequences with high yields. It is worth noting that CBApts exhibited significantly enhanced nuclease resistance, as well as considerably improved binding, targeting and tumor tissue enrichment abilities, which may pave the way for different investigations for biomedical purposes.

Anticancer-Active N-Heteroaryl Amines Syntheses: Nucleophilic Amination of N-Heteroaryl Alkyl Ethers with Amines.

A mild amination protocol of N-heteroaryl alkyl ethers with various amines is described. This transformation is achieved by utilizing simple and readily available base as promoter via C-O bond cleavage, offering a new amination strategy to access several anticancer-active compounds. This work is highlighted by the excellent functional group compatibility, scalability, wide substrate scope, and easy derivatization of a variety of drugs.

BF211, a derivative of bufalin, enhances the cytocidal effects in multiple myeloma cells by inhibiting the IL-6/JAK2/STAT3 pathway.

Despite remarkable advances in multiple myeloma (MM) therapy, this condition remains incurable. BF211 is an active compound derived from bufalin, which is isolated from the Traditional Chinese Medicine, Chansu. In this study, we explored the cytotoxicity of BF211 in 20 tumor cell lines and discovered that the MM cell lines, ARP-1 and CAG, exhibited greater sensitivity to BF211. Compared with bufalin, BF211 induced a greater apoptotic effect and lower acute toxicity at nanomolar concentration. The IL-6/JAK2/STAT3 signaling pathway is essential to the progression and development of MM. We showed that exogenous IL-6 promoted MM cell proliferation in a dose-dependent manner and this effect was blocked by BF211. Furthermore, BF211 suppressed the phosphorylation of JAK2 and STAT3 both in vivo and in vitro. In a mouse MM xenograft model, BF211 significantly inhibited tumor growth and did not affect body weight. In conclusion, the anti-MM activity of BF211 is mediated mainly by suppressing the IL-6/JAK2/STAT3 signaling pathway. Thus, we suggest that BF211 warrants further investigation in clinical trials in MM.