15345-89-8Relevant articles and documents
Synthetic kavalactone analogues with increased potency and selective anthelmintic activity against larvae of haemonchus contortus in vitro
Chang, Bill C. H.,Dilrukshi Herath, H. M. P.,Garcia-Bustos, José,Gasser, Robin B.,Hofmann, Andreas,Jabbar, Abdul,Ma, Guangxu,Nguyen, Nghi,Sleebs, Brad E.,Taki, Aya C.,Wang, Tao
, (2020)
Kava extract, an aqueous rhizome emulsion of the plant Piper methysticum, has been used for centuries by Pacific Islanders as a ceremonial beverage, and has been sold as an anxiolytic agent for some decades. Kavalactones are a major constituent of kava extract. In a previous investigation, we had identified three kavalactones that inhibit larval development of Haemonchus contortus in an in vitro-bioassay. In the present study, we synthesized two kavalactones, desmethoxyyangonin and yangonin, as well as 17 analogues thereof, and evaluated their anthelmintic activities using the same bioassay as employed previously. Structure activity relationship (SAR) studies showed that a 4-substituent on the pendant aryl ring was required for activity. In particular, compounds with 4-trifluoromethoxy, 4-difluoromethoxy, 4-phenoxy, and 4-N-morpholine substitutions had anthelmintic activities (IC50 values in the range of 1.9 to 8.9 μM) that were greater than either of the parent natural products-desmethoxyyangonin (IC50 of 37.1 μM) and yangonin (IC50 of 15.0 μM). The synthesized analogues did not exhibit toxicity on HepG2 human hepatoma cells in vitro at concentrations of up to 40 μM. These findings confirm the previously-identified kavalactone scaffold as a promising chemotype for new anthelmintics and provide a basis for a detailed SAR investigation focused on developing a novel anthelmintic agent.
Regioselective functionalization of pyrones: Facile synthesis of 6-styrylpyrones via KHMDS-mediated aldol condensation
Basu, Manas K.,Mukkanti, K.,Samala, Ramakrishna
, (2022/01/03)
Herein, we disclose our efforts directed toward the synthesis of the kavalactone-based natural product penstyrylpyrone and other related 4-OMe-2-pyrones possessing diverse substituents at the 3-, 5-, and 7-positions. Further, a facile approach to access 6-styrylpyrones via the KHMDS-mediated regioselective aldol condensation of 2-pyrones is described with moderate substrate scope and good to high yields (58–80%). The utility of this methodology was exemplified by the stereoselective construction of desmethoxyyangonin, asnipyrone A, and asnipyrone B.
Synthesis of novel 5,6-dehydrokawain analogs as osteogenic inducers and their action mechanisms
Kumagai, Momochika,Nishikawa, Keisuke,Mishima, Takashi,Yoshida, Izumi,Ide, Masahiro,Koizumi, Keiko,Nakamura, Munetomo,Morimoto, Yoshiki
supporting information, p. 2401 - 2406 (2017/05/09)
An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity. Among the potential analogs we synthesized, (E)-6-(4-Ethylstyryl)-4-methoxy-2H-pyran-2-one (14) and (E)-6-(4-Butylstyryl)-4-methoxy-2H-pyran-2-one (21) both significantly up-regulated Runx2 and Osterix mRNA expression at 10?μM. These osteogenic activities could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast differentiation of RAW264 cells. These results indicated that novel 5,6-dehydrokawain analogs not only increase osteogenic activity but also inhibit osteoclast differentiation, and could be potential lead compounds for the development of anti-osteoporosis agents.
