TY - JOUR
T1 - Synthesis and anthelmintic activity of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives
AU - Milišiūnaitė, Vaida
AU - Kadlecová, Alena
AU - Žukauskaitė, Asta
AU - Doležal, Karel
AU - Strnad, Miroslav
AU - Voller, Jiří
AU - Arbačiauskienė, Eglė
AU - Holzer, Wolfgang
AU - Šačkus, Algirdas
N1 - Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Abstract: A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing O-acylation, Fries rearrangement and potassium carbonate-induced cyclization. The anthelmintic properties of the obtained compounds were investigated in vivo in a model nematode, Caenorhabditis elegans. Five compounds, namely 2-phenyl[1]benzopyrano[2,3-c]pyrazol-4(2H)-one 33 and its 7-fluoro, 7-chloro-, 7-bromo- and 8-fluoro-analogues, 36, 38, 40 and 43, respectively, altered the development of C. elegans. While the activities of 33 and 43 were rather modest, compounds 36, 38 and 40 inhibited the growth of the worms at concentrations of approximately 1-3 µM. At these concentrations, the compounds did not kill the worms, but they strongly inhibited their development, with the majority of larvae never progressing past the L1 stage. Moreover, testing in non-cancer human cell lines showed that, with exception of 7-bromo derivative 40, the active compounds have favourable toxicity profiles. Graphic abstract: [Figure not available: see fulltext.]
AB - Abstract: A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing O-acylation, Fries rearrangement and potassium carbonate-induced cyclization. The anthelmintic properties of the obtained compounds were investigated in vivo in a model nematode, Caenorhabditis elegans. Five compounds, namely 2-phenyl[1]benzopyrano[2,3-c]pyrazol-4(2H)-one 33 and its 7-fluoro, 7-chloro-, 7-bromo- and 8-fluoro-analogues, 36, 38, 40 and 43, respectively, altered the development of C. elegans. While the activities of 33 and 43 were rather modest, compounds 36, 38 and 40 inhibited the growth of the worms at concentrations of approximately 1-3 µM. At these concentrations, the compounds did not kill the worms, but they strongly inhibited their development, with the majority of larvae never progressing past the L1 stage. Moreover, testing in non-cancer human cell lines showed that, with exception of 7-bromo derivative 40, the active compounds have favourable toxicity profiles. Graphic abstract: [Figure not available: see fulltext.]
KW - Anthelmintic activity
KW - Benzopyrano[2,3-c]pyrazol-4(2H)-ones
KW - Caenorhabditis elegans
KW - Cytotoxicity
KW - Pyrazole
UR - http://www.scopus.com/inward/record.url?scp=85075142598&partnerID=8YFLogxK
U2 - 10.1007/s11030-019-10010-3
DO - 10.1007/s11030-019-10010-3
M3 - Article
C2 - 31713185
AN - SCOPUS:85075142598
SN - 1381-1991
VL - 24
SP - 1025
EP - 1042
JO - Molecular Diversity
JF - Molecular Diversity
IS - 4
ER -