Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds

Esther Del Olmo; Bianca Barboza; Louise D. Chiaradia; Alicia Moreno; Juana Carrero-Lérida; Dolores González-Pacanowska; Victoria Muñoz; José L. López-Pérez; Alberto Giménez; Agustín Benito; Antonio R. Martínez; Luis M. Ruiz-Pérez; Arturo San Feliciano

doi:10.1016/j.ejmech.2011.08.043

Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds

Esther Del Olmo, Bianca Barboza, Louise D. Chiaradia, Alicia Moreno, Juana Carrero-Lérida, Dolores González-Pacanowska, Victoria Muñoz, José L. López-Pérez, Alberto Giménez, Agustín Benito, Antonio R. Martínez, Luis M. Ruiz-Pérez, Arturo San Feliciano

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

20 Scopus citations

Abstract

The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC ₅₀ values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.

Original language	English
Pages (from-to)	5379-5386
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	46
Issue number	11
DOIs	https://doi.org/10.1016/j.ejmech.2011.08.043
State	Published - Nov 2011

Bibliographical note

Funding Information:
Authors thank Dr. Carmen Cuevas (PharmaMar S.A. Madrid, Spain) for cytotoxicity assays and to Bioinformatic & Molecular Design Research Center (BMDRC, Yonsey University, Seoul, Korea) for complimentary access to preADMET database. BB and LDC thank the respective fellowships from ALFA (ALR/B73011/94.04-6.0275.9) and ALBAN (E07D401988BR) EC Programs. Financial support from FIS-PI-060782 , FIS-PI-052026 , SAF2010-20059 , the “Plan Andaluz de Investigación (BIO199 )” and ISCIII-RICET ( RD06/0021: 0000 , 0018, 0022 ) is also acknowledged.

Keywords

Imidazoisoindoles
In vitro assays
In vivo assays
Mouse model
Plasmodium berghei
Plasmodium falciparum
Structure-activity relationship
Synthesis

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Olmo, E. D., Barboza, B., Chiaradia, L. D., Moreno, A., Carrero-Lérida, J., González-Pacanowska, D., Muñoz, V., López-Pérez, J. L., Giménez, A., Benito, A., Martínez, A. R., Ruiz-Pérez, L. M., & San Feliciano, A. (2011). Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds. European Journal of Medicinal Chemistry, 46(11), 5379-5386. https://doi.org/10.1016/j.ejmech.2011.08.043

@article{2a81c690548140508a1f0a5de6566749,

title = "Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds",

abstract = "The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC 50 values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.",

keywords = "Imidazoisoindoles, In vitro assays, In vivo assays, Mouse model, Plasmodium berghei, Plasmodium falciparum, Structure-activity relationship, Synthesis",

author = "Olmo, {Esther Del} and Bianca Barboza and Chiaradia, {Louise D.} and Alicia Moreno and Juana Carrero-L{\'e}rida and Dolores Gonz{\'a}lez-Pacanowska and Victoria Mu{\~n}oz and L{\'o}pez-P{\'e}rez, {Jos{\'e} L.} and Alberto Gim{\'e}nez and Agust{\'i}n Benito and Mart{\'i}nez, {Antonio R.} and Ruiz-P{\'e}rez, {Luis M.} and {San Feliciano}, Arturo",

note = "Funding Information: Authors thank Dr. Carmen Cuevas (PharmaMar S.A. Madrid, Spain) for cytotoxicity assays and to Bioinformatic & Molecular Design Research Center (BMDRC, Yonsey University, Seoul, Korea) for complimentary access to preADMET database. BB and LDC thank the respective fellowships from ALFA (ALR/B73011/94.04-6.0275.9) and ALBAN (E07D401988BR) EC Programs. Financial support from FIS-PI-060782 , FIS-PI-052026 , SAF2010-20059 , the “Plan Andaluz de Investigaci{\'o}n (BIO199 )” and ISCIII-RICET ( RD06/0021: 0000 , 0018, 0022 ) is also acknowledged. ",

year = "2011",

month = nov,

doi = "10.1016/j.ejmech.2011.08.043",

language = "Ingl{\'e}s",

volume = "46",

pages = "5379--5386",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

number = "11",

}

Olmo, ED, Barboza, B, Chiaradia, LD, Moreno, A, Carrero-Lérida, J, González-Pacanowska, D, Muñoz, V, López-Pérez, JL, Giménez, A, Benito, A, Martínez, AR, Ruiz-Pérez, LM & San Feliciano, A 2011, 'Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds', European Journal of Medicinal Chemistry, vol. 46, no. 11, pp. 5379-5386. https://doi.org/10.1016/j.ejmech.2011.08.043

TY - JOUR

T1 - Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds

AU - Olmo, Esther Del

AU - Barboza, Bianca

AU - Chiaradia, Louise D.

AU - Moreno, Alicia

AU - Carrero-Lérida, Juana

AU - González-Pacanowska, Dolores

AU - Muñoz, Victoria

AU - López-Pérez, José L.

AU - Giménez, Alberto

AU - Benito, Agustín

AU - Martínez, Antonio R.

AU - Ruiz-Pérez, Luis M.

AU - San Feliciano, Arturo

N1 - Funding Information: Authors thank Dr. Carmen Cuevas (PharmaMar S.A. Madrid, Spain) for cytotoxicity assays and to Bioinformatic & Molecular Design Research Center (BMDRC, Yonsey University, Seoul, Korea) for complimentary access to preADMET database. BB and LDC thank the respective fellowships from ALFA (ALR/B73011/94.04-6.0275.9) and ALBAN (E07D401988BR) EC Programs. Financial support from FIS-PI-060782 , FIS-PI-052026 , SAF2010-20059 , the “Plan Andaluz de Investigación (BIO199 )” and ISCIII-RICET ( RD06/0021: 0000 , 0018, 0022 ) is also acknowledged.

PY - 2011/11

Y1 - 2011/11

N2 - The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC 50 values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.

AB - The synthesis of several series of imidazo[2,1-a]isoindol-5-ol derivatives and the results of their evaluation against Plasmodium falciparum are presented and discussed. The effects of electron-withdrawing or-donating substituents on different parts of the molecule, as well as those produced by the incorporation of an additional fused ring, were analyzed. Several compounds showed significant antimalarial activity in vitro with IC 50 values as low as 60 nM and a certain efficacy in vivo by reducing parasitemia in Plasmodium berghei mouse models.

KW - Imidazoisoindoles

KW - In vitro assays

KW - In vivo assays

KW - Mouse model

KW - Plasmodium berghei

KW - Plasmodium falciparum

KW - Structure-activity relationship

KW - Synthesis

UR - http://www.scopus.com/inward/record.url?scp=80054907453&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2011.08.043

DO - 10.1016/j.ejmech.2011.08.043

M3 - Artículo

C2 - 21940072

AN - SCOPUS:80054907453

SN - 0223-5234

VL - 46

SP - 5379

EP - 5386

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

IS - 11

ER -

Antimalarial activity of imidazo[2,1-a]isoindol-5-ol derivatives and related compounds

Abstract

Bibliographical note

Keywords

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