Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

C. Brullo; F. Rapetti; S. Alfei; I. Maric; F. Rizzelli; M. Mapelli; C. Rosano; M. Viale; O. Bruno

doi:10.1002/cmdc.202000122

Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

C. Brullo, F. Rapetti, S. Alfei, I. Maric, F. Rizzelli, M. Mapelli, C. Rosano, M. Viale, O. Bruno

Research output: Contribution to journal › Article › peer-review

Abstract

Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Original language	English
Pages (from-to)	961-969
Number of pages	9
Journal	ChemMedChem
Volume	15
Issue number	11
DOIs	https://doi.org/10.1002/cmdc.202000122
Publication status	Published - 2020

Keywords

antiproliferative agents
apoptosis
cell cycle inhibition
imidazo[1,2-b]pyrazole acylhydrazones
tubuline polymerization.
5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 benzyloxy 4 methoxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 benzyloxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 methoxy 4 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (3,4 dimethoxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 benzyloxy 3 methoxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 benzyloxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 fluoro 3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 methoxy 3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide
5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide
antineoplastic agent
benzylidene derivative
colchicine
hydrazide derivative
imidazole derivative
n' (3 benzyloxy 4 methoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (3 benzyloxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (3 methoxy 2 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (3 methoxy 4 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (3 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (3,4 dimethoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (4 benzyloxy 3 methoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (4 benzyloxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (4 methoxy 3 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
n' (4 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide
nocodazole
pyrazole derivative
tubulin
unclassified drug
vinblastine
786-O cell line
A-549 cell line
A2780 cell line
antiproliferative activity
Article
cancer inhibition
cell cycle G0 phase
cell cycle G1 phase
cell cycle G2 phase
cell cycle M phase
cell cycle S phase
cell interaction
cell proliferation
controlled study
drug efficacy
drug mechanism
drug potency
drug synthesis
drug targeting
female
HT-29 cell line
human
human cell
IC50
immunofluorescence
IMR-32 cell line
LC50
LOX-IMVI cell line
male
MDA-MB-435 cell line
MDA-MB-453 cell line
microtubule
microtubule assembly
multinuclear cell
NCI-H460 cell line
OVCAR-3 cell line
OVCAR-4 cell line
PC-3 [Human prostate carcinoma] cell line
preliminary data
priority journal
proapoptotic activity
SF295 cell line
SF539 cell line
SK-BR-3 cell line
SNB-75 cell line
structure activity relation
SW620 cell line
T-47D cell line
tubulin polymerization assay
U-251MG cell line

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10.1002/cmdc.202000122

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084135034&doi=10.1002%2fcmdc.202000122&partnerID=40&md5=fee6b9629ee256b62d5d6e45710cf2d3

Cite this

@article{930d946fc1b144daa0c14ae051b054d3,

title = "Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems",

abstract = "Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. {\textcopyright} 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

keywords = "antiproliferative agents, apoptosis, cell cycle inhibition, imidazo[1,2-b]pyrazole acylhydrazones, tubuline polymerization., 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 benzyloxy 4 methoxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 benzyloxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 methoxy 4 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3,4 dimethoxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 benzyloxy 3 methoxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 benzyloxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 fluoro 3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 methoxy 3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide, 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide, antineoplastic agent, benzylidene derivative, colchicine, hydrazide derivative, imidazole derivative, n' (3 benzyloxy 4 methoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (3 benzyloxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (3 methoxy 2 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (3 methoxy 4 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (3 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (3,4 dimethoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (4 benzyloxy 3 methoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (4 benzyloxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (4 methoxy 3 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, n' (4 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide, nocodazole, pyrazole derivative, tubulin, unclassified drug, vinblastine, 786-O cell line, A-549 cell line, A2780 cell line, antiproliferative activity, Article, cancer inhibition, cell cycle G0 phase, cell cycle G1 phase, cell cycle G2 phase, cell cycle M phase, cell cycle S phase, cell interaction, cell proliferation, controlled study, drug efficacy, drug mechanism, drug potency, drug synthesis, drug targeting, female, HT-29 cell line, human, human cell, IC50, immunofluorescence, IMR-32 cell line, LC50, LOX-IMVI cell line, male, MDA-MB-435 cell line, MDA-MB-453 cell line, microtubule, microtubule assembly, multinuclear cell, NCI-H460 cell line, OVCAR-3 cell line, OVCAR-4 cell line, PC-3 [Human prostate carcinoma] cell line, preliminary data, priority journal, proapoptotic activity, SF295 cell line, SF539 cell line, SK-BR-3 cell line, SNB-75 cell line, structure activity relation, SW620 cell line, T-47D cell line, tubulin polymerization assay, U-251MG cell line",

author = "C. Brullo and F. Rapetti and S. Alfei and I. Maric and F. Rizzelli and M. Mapelli and C. Rosano and M. Viale and O. Bruno",

note = "Export Date: 2 March 2021 CODEN: CHEMG Correspondence Address: Brullo, C.; Department of Pharmacy, V.le Benedetto XV, 3, Italy; email: brullo@difar.unige.it Chemicals/CAS: colchicine, 64-86-8; nocodazole, 31430-18-9; vinblastine, 865-21-4 Funding details: National Cancer Institute, NCI Funding text 1: The authors thank NCI, Division of Cancer Treatment Diagnosis (USA), for screening the title compounds during the Developmental Therapeutic Program (DPI) and Dr. R. Raggio, Dr. M. Anzaldi, and O. Gagliardo for technical support. References: Brullo, C., Spisani, S., Selvatici, R., Bruno, O., (2012) Eur. J. Med. Chem., 47, pp. 573-579; Selvatici, R., Brullo, C., Bruno, O., Spisani, S., (2013) Eur. J. Pharm. Sci., 718, pp. 428-434; Meta, E., Brullo, C., Sidibe, A., Imhof, B.A., Bruno, O., (2017) Eur. J. Med. Chem., 133, pp. 24-35; Meta, E., Imhof, B.A., Ropraz, P., Fish, R.J., Brullo, C., Bruno, O., Sidib{\'e}, A., (2017) Oncotarget, 8, pp. 108195-108212; Qin, T., Chen, F., Zhuo, X., Guo, X., Yun, T., Liu, Y., Zhang, C., Lai, L., (2016) J. Med. Chem., 59, pp. 7089-7096; Rodrigues, D.A., Ferreira-Silva, G.A., Ferreira, A.C.S., Fernandes, R.A., Kwee, J.K., Sant'Anna, C.M.R., Ionta, M., Fraga, C.A.M., (2016) J. Med. Chem., 59, pp. 655-670; Zuercher, W.J., Gaillard, S., Orband-Miller, L.A., Chao, E.Y.H., Shearer, B.G., Jones, D.G., Miller, A.B., Willson, T.M., (2005) J. Med. Chem., 48, pp. 3107-3109; Sorna, V., Theisen, E.R., Stephens, B., Warner, S.L., Bearss, D.J., Vankayalapati, H., Sharma, S., (2013) J. Med. Chem., 56, pp. 9496-9508; Bondavalli, F., Botta, M., Bruno, O., Ciacci, A., Corelli, F., Fossa, P., Lucacchini, A., Trincavelli, M.L., (2002) J. Med. Chem., 45, pp. 4875-4887; Bruno, O., Brullo, C., Bondavalli, F., Ranise, A., Schenone, S., Falzarano, M.S., Varani, K., Spisani, S., (2007) BMCL, 17, pp. 3696-3701; Crowder, J.R., Glover, E.E., Grundon, M.F., Kaempfen, H.X., (1963) J. Chem. Soc., pp. 4578-4585; Ashton, M.J., Cook, D.C., Fenton, G., Karlsson, J.A., Palfreyman, M.N., Raeburn, D., Ratcliffe, A.J., Vicker, N., (1994) J. Med. Chem., 37, pp. 1696-1703; Brullo, C., Massa, M., Rapetti, F., Alfei, S., Bertolotto, M.B., Montecucco, F., Signorello, M.G., Bruno, O., (2020) Molecules, 25, p. 899; Goh, E.L.K., Pircher, T.J., Lobie, P.E., (1998) Endocrinology, 139, pp. 4364-4372; Balbi, A., Anzaldi, M., Macci{\`o}, C., Aiello, C., Mazzei, M., Gangemi, R., Castagnola, P., Viale, M., (2011) Eur. J. Med. Chem., 46, pp. 5293-5309; Slep, K.C., Vale, R.D., (2007) Mol. Cell, 27, pp. 976-991; Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J., (2009) J. Comput. Chem., 16, pp. 2785-2791; Waight, A.B., Bargsten, K., Doronina, S., Steinmetz, M.O., Sussman, D., Prota, A.E., (2016) PLoS One, 11; Shelanski, M.L., Gaskin, F., Cantor, C.R., (1973) Proc. Natl. Acad. Sci. USA, 70, pp. 765-768; Lee, J.C., Timasheff, S.N., (1977) Biochemistry, 16, pp. 1754-1764; Dell'Erba, C., Chiavarina, B., Fenoglio, C., Petrillo, G., Cordazzo, C., Boncompagni, E., Spinelli, D., Viale, M., (2005) Pharmacol. Res., 52, pp. 271-282; Pettersen, E.F., Goddard, T.D., Huagn, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., (2004) J. Comput. Chem., 25, pp. 1605-1612",

year = "2020",

doi = "10.1002/cmdc.202000122",

language = "English",

volume = "15",

pages = "961--969",

journal = "ChemMedChem",

issn = "1860-7179",

publisher = "John Wiley and Sons Ltd",

number = "11",

}

TY - JOUR

T1 - Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

AU - Brullo, C.

AU - Rapetti, F.

AU - Alfei, S.

AU - Maric, I.

AU - Rizzelli, F.

AU - Mapelli, M.

AU - Rosano, C.

AU - Viale, M.

AU - Bruno, O.

N1 - Export Date: 2 March 2021 CODEN: CHEMG Correspondence Address: Brullo, C.; Department of Pharmacy, V.le Benedetto XV, 3, Italy; email: brullo@difar.unige.it Chemicals/CAS: colchicine, 64-86-8; nocodazole, 31430-18-9; vinblastine, 865-21-4 Funding details: National Cancer Institute, NCI Funding text 1: The authors thank NCI, Division of Cancer Treatment Diagnosis (USA), for screening the title compounds during the Developmental Therapeutic Program (DPI) and Dr. R. Raggio, Dr. M. Anzaldi, and O. Gagliardo for technical support. References: Brullo, C., Spisani, S., Selvatici, R., Bruno, O., (2012) Eur. J. Med. Chem., 47, pp. 573-579; Selvatici, R., Brullo, C., Bruno, O., Spisani, S., (2013) Eur. J. Pharm. Sci., 718, pp. 428-434; Meta, E., Brullo, C., Sidibe, A., Imhof, B.A., Bruno, O., (2017) Eur. J. Med. Chem., 133, pp. 24-35; Meta, E., Imhof, B.A., Ropraz, P., Fish, R.J., Brullo, C., Bruno, O., Sidibé, A., (2017) Oncotarget, 8, pp. 108195-108212; Qin, T., Chen, F., Zhuo, X., Guo, X., Yun, T., Liu, Y., Zhang, C., Lai, L., (2016) J. Med. Chem., 59, pp. 7089-7096; Rodrigues, D.A., Ferreira-Silva, G.A., Ferreira, A.C.S., Fernandes, R.A., Kwee, J.K., Sant'Anna, C.M.R., Ionta, M., Fraga, C.A.M., (2016) J. Med. Chem., 59, pp. 655-670; Zuercher, W.J., Gaillard, S., Orband-Miller, L.A., Chao, E.Y.H., Shearer, B.G., Jones, D.G., Miller, A.B., Willson, T.M., (2005) J. Med. Chem., 48, pp. 3107-3109; Sorna, V., Theisen, E.R., Stephens, B., Warner, S.L., Bearss, D.J., Vankayalapati, H., Sharma, S., (2013) J. Med. Chem., 56, pp. 9496-9508; Bondavalli, F., Botta, M., Bruno, O., Ciacci, A., Corelli, F., Fossa, P., Lucacchini, A., Trincavelli, M.L., (2002) J. Med. Chem., 45, pp. 4875-4887; Bruno, O., Brullo, C., Bondavalli, F., Ranise, A., Schenone, S., Falzarano, M.S., Varani, K., Spisani, S., (2007) BMCL, 17, pp. 3696-3701; Crowder, J.R., Glover, E.E., Grundon, M.F., Kaempfen, H.X., (1963) J. Chem. Soc., pp. 4578-4585; Ashton, M.J., Cook, D.C., Fenton, G., Karlsson, J.A., Palfreyman, M.N., Raeburn, D., Ratcliffe, A.J., Vicker, N., (1994) J. Med. Chem., 37, pp. 1696-1703; Brullo, C., Massa, M., Rapetti, F., Alfei, S., Bertolotto, M.B., Montecucco, F., Signorello, M.G., Bruno, O., (2020) Molecules, 25, p. 899; Goh, E.L.K., Pircher, T.J., Lobie, P.E., (1998) Endocrinology, 139, pp. 4364-4372; Balbi, A., Anzaldi, M., Macciò, C., Aiello, C., Mazzei, M., Gangemi, R., Castagnola, P., Viale, M., (2011) Eur. J. Med. Chem., 46, pp. 5293-5309; Slep, K.C., Vale, R.D., (2007) Mol. Cell, 27, pp. 976-991; Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J., (2009) J. Comput. Chem., 16, pp. 2785-2791; Waight, A.B., Bargsten, K., Doronina, S., Steinmetz, M.O., Sussman, D., Prota, A.E., (2016) PLoS One, 11; Shelanski, M.L., Gaskin, F., Cantor, C.R., (1973) Proc. Natl. Acad. Sci. USA, 70, pp. 765-768; Lee, J.C., Timasheff, S.N., (1977) Biochemistry, 16, pp. 1754-1764; Dell'Erba, C., Chiavarina, B., Fenoglio, C., Petrillo, G., Cordazzo, C., Boncompagni, E., Spinelli, D., Viale, M., (2005) Pharmacol. Res., 52, pp. 271-282; Pettersen, E.F., Goddard, T.D., Huagn, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., Ferrin, T.E., (2004) J. Comput. Chem., 25, pp. 1605-1612

PY - 2020

Y1 - 2020

N2 - Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

AB - Even though immunotherapy has radically changed the search for anticancer therapies, there are still many different pathways that are open to intervention with traditional small molecules. To expand our investigation in the anticancer field, we report here a new series of compounds in which our previous pyrazole and imidazopyrazole scaffolds are linked to a differently decorated phenyl ring through an acylhydrazone linker. Preliminary tests on the library were performed at the National Cancer Institute (USA) against the full NCI 60 cell panel. The best compounds among the imidazopyrazole series were then tested by immunofluorescence staining for their inhibition of cell proliferation, apoptosis induction, and their effect on the cell cycle and on microtubules. Two compounds, in particular 4-benzyloxy-3-methoxybenzyliden imidazopyrazole-7-carbohydrazide showed good growth inhibition, with IC50 values in the low-micromolar range, and induced apoptosis. Both compounds altered the cell-cycle phases with the appearance of polyploid cells. Immunofluorescence analysis evidenced microtubules alterations; tubulin polymerization assays and docking studies suggested the tubulin system to be the possible, although not exclusive, target of the new acylhydrazone series reported here. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

KW - antiproliferative agents

KW - apoptosis

KW - cell cycle inhibition

KW - imidazo[1,2-b]pyrazole acylhydrazones

KW - tubuline polymerization.

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 benzyloxy 4 methoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 benzyloxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 methoxy 4 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (3,4 dimethoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 benzyloxy 3 methoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 benzyloxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 fluoro 3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 methoxy 3 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - 5 amino 1 (2 hydroxy 2 phenylethyl) n' (4 phenoxybenzylidene) 1h pyrazole 4 carbohydrazide

KW - antineoplastic agent

KW - benzylidene derivative

KW - colchicine

KW - hydrazide derivative

KW - imidazole derivative

KW - n' (3 benzyloxy 4 methoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (3 benzyloxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (3 methoxy 2 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (3 methoxy 4 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (3 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (3,4 dimethoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (4 benzyloxy 3 methoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (4 benzyloxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (4 methoxy 3 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - n' (4 phenoxybenzylidene) 2 phenyl 2,3 dihydro 1h imidazo[1,2 b]pyrazole 7 carbohydrazide

KW - nocodazole

KW - pyrazole derivative

KW - tubulin

KW - unclassified drug

KW - vinblastine

KW - 786-O cell line

KW - A-549 cell line

KW - A2780 cell line

KW - antiproliferative activity

KW - Article

KW - cancer inhibition

KW - cell cycle G0 phase

KW - cell cycle G1 phase

KW - cell cycle G2 phase

KW - cell cycle M phase

KW - cell cycle S phase

KW - cell interaction

KW - cell proliferation

KW - controlled study

KW - drug efficacy

KW - drug mechanism

KW - drug potency

KW - drug synthesis

KW - drug targeting

KW - female

KW - HT-29 cell line

KW - human

KW - human cell

KW - IC50

KW - immunofluorescence

KW - IMR-32 cell line

KW - LC50

KW - LOX-IMVI cell line

KW - male

KW - MDA-MB-435 cell line

KW - MDA-MB-453 cell line

KW - microtubule

KW - microtubule assembly

KW - multinuclear cell

KW - NCI-H460 cell line

KW - OVCAR-3 cell line

KW - OVCAR-4 cell line

KW - PC-3 [Human prostate carcinoma] cell line

KW - preliminary data

KW - priority journal

KW - proapoptotic activity

KW - SF295 cell line

KW - SF539 cell line

KW - SK-BR-3 cell line

KW - SNB-75 cell line

KW - structure activity relation

KW - SW620 cell line

KW - T-47D cell line

KW - tubulin polymerization assay

KW - U-251MG cell line

U2 - 10.1002/cmdc.202000122

DO - 10.1002/cmdc.202000122

M3 - Article

VL - 15

SP - 961

EP - 969

JO - ChemMedChem

JF - ChemMedChem

SN - 1860-7179

IS - 11

ER -

Discovery of New Antiproliferative Imidazopyrazole Acylhydrazones Able To Interact with Microtubule Systems

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