European Journal of Medicinal Chemistry, volume 92, pages 866-875

Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents

Juan Gabriel Ramirez ¹

Laura A. Svetaz ²

Jairo Quiroga ¹

Rodrigo Abonia ¹

Marcela Raimondi ²

Susana Zacchino ²

Braulio Insuasty ¹

Hide authors affiliations Show authors affiliations: 2 affiliations

Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, AA 25360 Cali, Colombia |

Area Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina. |

Publication type: Journal Article

Publication date: 2015-03-01

Elsevier

Journal: European Journal of Medicinal Chemistry

Quartile SCImago

Quartile WOS

Impact factor: 6.7

ISSN: 02235234, 17683254

DOI: 10.1016/j.ejmech.2015.01.053

Copy DOI

Organic Chemistry

Drug Discovery

General Medicine

Pharmacology

Abstract

A new series of novel thiazole-based 8,9-dihydro-7 H -pyrimido[4,5- b ][1,4]diazepines 6a – g and 7a – g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,β-unsaturated carbonyl compounds 3a – g based on 2,4-dichlorothiazol-5-carbaldehyde 1 . Twelve of the synthesized compounds were selected and tested by US National Cancer Institute (NCI) for their antitumor activity against 60 different human tumor cell lines. Compounds 7d and 7g showed important GI 50 ranges of 1.28–2.98 μM and 0.35–2.78 μM respectively under in vitro assays. In addition, 6a – g and 7a – g were tested for antifungal properties against the clinical important fungi Candida albicans and Cryptococcus neoformans . Although these compounds showed moderate activities against C. albicans , the 2-amino derivatives 7a – g and mainly 7a and 7b , showed high activity against standardized and clinical isolates of C. neoformans with MIC 50 = 7.8–31.2 μg/mL, MIC 80 = 15.6–31.2 μg/mL and MIC 100 = 15.6–62.5 μg/mL. In addition, since both compounds were fungicide rather than fungistatic these thiazole-based 8,9-dihydro-7 H -pyrimido[4,5- b ][1,4]diazepines appear as good candidates for further development not only as antifungal but also as antitumor drugs. • New series of pyrimido[4,5- b ][1,4]diazepines were synthesized from caffeine. • All diazepines were obtained with high regioselectivity. • Compounds 7d and 7g showed important antitumor activity with GI 50 0.35–2.98 μM. • Antifungal activity was performed against C. albicans and C. neoformans . • Diazepines 7a and 7b exhibited high activity against clinical isolated C. neoformans .

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Hindawi Limited	Hindawi Limited, 1, 3.45% Hindawi Limited 1 publication, 3.45%
American Institute of Physics (AIP)	American Institute of Physics (AIP), 1, 3.45% American Institute of Physics (AIP) 1 publication, 3.45%
Thieme	Thieme, 1, 3.45% Thieme 1 publication, 3.45%
American Chemical Society (ACS)	American Chemical Society (ACS), 1, 3.45% American Chemical Society (ACS) 1 publication, 3.45%
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Ramirez J. G. et al. Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents // European Journal of Medicinal Chemistry. 2015. Vol. 92. pp. 866-875.

GOST all authors (up to 50) Copy

Ramirez J. G., Svetaz L. A., Quiroga J., Abonia R., Raimondi M., Zacchino S., Insuasty B. Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents // European Journal of Medicinal Chemistry. 2015. Vol. 92. pp. 866-875.

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RIS Copy

TY - JOUR

DO - 10.1016/j.ejmech.2015.01.053

UR - https://doi.org/10.1016/j.ejmech.2015.01.053

TI - Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents

T2 - European Journal of Medicinal Chemistry

AU - Ramirez, Juan Gabriel

AU - Svetaz, Laura A.

AU - Quiroga, Jairo

AU - Abonia, Rodrigo

AU - Raimondi, Marcela

AU - Zacchino, Susana

AU - Insuasty, Braulio

PY - 2015

DA - 2015/03/01 00:00:00

PB - Elsevier

SP - 866-875

VL - 92

SN - 0223-5234

SN - 1768-3254

ER -

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@article{2015_Ramirez,

author = {Juan Gabriel Ramirez and Laura A. Svetaz and Jairo Quiroga and Rodrigo Abonia and Marcela Raimondi and Susana Zacchino and Braulio Insuasty},

title = {Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents},

journal = {European Journal of Medicinal Chemistry},

year = {2015},

volume = {92},

publisher = {Elsevier},

month = {mar},

url = {https://doi.org/10.1016/j.ejmech.2015.01.053},

pages = {866--875},

doi = {10.1016/j.ejmech.2015.01.053}

}

Found error?

Publisher

Elsevier

Journal

European Journal of Medicinal Chemistry

Quartile SCImago

Quartile WOS

Impact factor

6.7

ISSN

02235234 (Print)
17683254 (Electronic)