Système gastro-intestinal et digestif

Abstrait

Digestive Diseases 2020: Total synthesis based on the natural furanonaphthoquinone scaffold and their biological activity evaluation: Chik Wai I - Hong Kong Baptist University

Chik Wai I

Furanonaphthoquinones (FNQs) are a group of small molecules that have been found to exhibit a variety of biological activities, including antimicrobial and anticancer activities. Their natural occurrence includes plants of the Bignoniaceae family. Bioactivity-guided fractionation and isolation of Rademacher boniana Dop led to the separation and identification of napabucasin, which is a cytotoxic FNQ that can selectively target cancer stemness and metastasis. The study of napabucasin has been extensive and according to the National Cancer Institute, napabucasin is currently involved in several active clinical trials for treating cancer, including advanced and metastatic colorectal cancer. To cope with the increasing Traditional and alternative   Medicine have long   been   used for treating   cancer. Cytotoxic phyto chemicals have been isolated from a vast variety of plants and herbal medicines and they have been developed into anti-cancer lead compound sand therapeutic drugs. Naphthoquinones (NQ) are composed   of a   ten-carbon   skeleton and appear   in   the   forms of 1,2-naphthoquinones and 1,4-naphthoquinones.Researchhas revealed their abilities in reducing cancer stemness and metastatic potential. A class of NQ derivatives is characterized by anaphthoquinone fused with a furanring and they  are  known  as furano-naphthoquinones  (FNQ).FNQs  have  demonstrated  a broad spectrum  of bioactivities  including  antitumor  and  antimalarial  effects. They  often  show  higher  efficacy when compared to  NQ sin  combating  pathological conditions, such  as avariety  of  cancers including leukemia,  breast,  colon  and lung  cancers. It is believed that FNQ can be further developed into new-generation chemotherapeutic agents. Radermachera  boniana  Dop (Figure  1) is  a Vietnam-based flowering  plant belonging  to  the Bignoniaceae family. Bioactivity-guided  fractionation  and  isolation led  to  the identification of napabucasin(BBI608), which has been regarded as a potential candidate for development of therapeutic drugs that can act directly  on cancer  stem  cells  (CSCs)to  overcome  the  problem of  chemotherapy resistance. BBI608 has aroused the interests of researchers in this area and relevant studies have been extensive. According to the National Cancer Institute, napabucasin is involved in several clinical trials foranti-cancer treatment; these include advanced and metastatic colorectal cancer. To  cope  with  the rising demand in obtaining the  compound  for  further research, a  facile  and economic  total  synthesis  route by utilizing easily.

Accessed reactants  as  starting materials for  the synthesis of FNQs has been established. Moreover, structurally modified FNQ derivatives and analogs can also be chemically synthesized with reference to the accomplished synthesis pathway. Examples are indole quinone derivatives    which    possess    nitrogen-containing hetero cycle instead    of oxygen-containing hetero cyclic FNQs. The cost of obtaining BBI608would be reduced by using the efficient total synthesis route and more derivatives  and analog scan be produced for structure-activity relationship (SAR) and mechanism of Total Synthesis Based on the Natural Furanonaphthoquinone Scaffold and their Biological Activity Evaluation[1] Chik Wai I, [2] Kwan Ming Lee, [3] Siu Wai Tsang, [4] HongJie Zhang[1]Hong Kong Baptist University－ Institute of Research and Continuing Education, Shenzhen Virtual University Park Shenzhen, China,[2] Department of Biology, Hong Kong Baptist University, Hong Kong SAR, P.R. China, [3]Hong Kong Baptist University－Institute of Research and Continuing Education, Shenzhen Virtual University Park Shenzhen, China,[4] School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P.R. China Colorectal cancer (CRC) is a disease with high incidence and mortality, constituting the fourth most common cause of death from cancer worldwide. Naphthoquinones are attractive compounds due to their biological and structural properties. In this work, 36 naphthoquinone derivatives were synthesized and their activity evaluated against HT-29 cells. Overall, high to moderate anti-proliferative activity was observed in most members of the series demand of an effective synthesis resulting in the generation of a reliable model (r2 = 0.99 and q2 = 0.625). This model allowed proposing five new compounds with two-fold higher theoretical anti-proliferative activity, which would be worthwhile to synthesize and evaluate. Further investigations will be needed to determine the mechanism involved in the effect of most active compounds which are potential candidates for new anticancer agents approach for the lead compound for its further development into a drug candidate, a facile and economic total synthesis route has been established. Moverover, derivatives of napabucasin have been synthesized in order to study the structure-activity relationship (SAR) so as to provide evidence for lead optimization and also for unraveling the mechanism of action