Izvestiya of Saratov University.

Chemistry. Biology. Ecology

ISSN 1816-9775 (Print)
ISSN 2541-8971 (Online)

Full text:
(downloads: 112)
Article type: 

Comparison of Cytotoxic Activity of Compounds from the Benzimidazolequinazoline and Pyridopyrimidine Series

Ivonin Maksim Andreevich, Saratov State University
Fomin Alexander S., Institute of Biochemistry and Physiology of Plants and Microorganisms of the Russian Academy of Sciences
Burygin Gennady L., Institute of Biochemistry and Physiology of Plants and Microorganisms of the Russian Academy of Sciences
Sorokin Vitaly Viktorovich, Saratov State University

Colorimetrically using the MTT assay the cytotoxic activity of 5-aryl-1,2,3,4,5,6-hexahydrobenz[4,5]imidazolo[1,2-a]quinazolines and a tautomeric mixture of 4-amino-2-phenyl-6H-pyrido[1,2-a] pyrimidin-3-carbonitrile with 2-(phenyl(pyridin-2-ylamino)methyl)- malononitrile was screened. These compounds were obtained by the three-component condensation of aromatic aldehydes (benzaldehyde, 3-bromobenzaldehyde, 4-methoxybenzaldehyde), heterocyclic amines (2-aminobenzimidazole or 2-aminopyridine) and cyclohexanone or malonic acid dinitrile in comparison with the starting amines. Compounds were tested at concentrations of 100, 50, 25, 12.5, 6.25, 3.12, and 1.61 ?g/ml on monolayer cell lines of the African green monkey kidney (Vero). IC50 values for the most active compounds (5-(4-methoxyphenyl)-1,2,3,4,5,6- hexahydrobenz[4,5]imidazolo[1,2-a]quinazoline and a tautomeric mixture of 4-amino-2-aryl-6H-pyrido[1,2-a]pyrimidine-3-carbonitrile with 2-(phenyl(pyridin-2-ylamino)methyl)-malononitrile were 75 and 50 ?g/ml, respectively. For 5-phenyl-1,2,3,4,5,6-hexahydrobenz[4,5] imidazolo[1,2-a]quinazoline, the IC50 value was 100 ?g/ml. For the remaining compounds, IC50 was not detected, and the starting 2-aminobenzimidazole and 2-aminopyridine inhibited the metabolic activity by only 20–30% at maximum concentrations. The values of the half-inhibitory concentration determined using the MTT assay are similar to the values, which were obtained earlier in the cytotoxic studies of similar heterocyclic compounds by AlamarBlue assay.

  1. Hermecz I., Horvath A., Rodriguez L., Meszaros Z. Nitrogen bridgehead compounds. 44. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones // Journal of Medicinal Chemistry. 1984. Vol. 27, №. 10. P. 1253–1259. DOI: https://doi.org/10.1021/jm00376a003
  2. Donkor I. O., Klein C. L., Liang L., Zhu N. Synthesis and antimicrobial activity of 6,7-annulated pyrido[2,3-d] pyrimidines // Journal of Pharmaceutical Sciences. 1995. Vol. 84, № 5. P. 661–664. DOI: https://doi.org/10.1002/jps.2600840526
  3. Thompson A. M., Bridges A. J., Fry D. W. Tyrosine kinase inhibitors. 7-Amino-4-(phenylamino)-and 7-amino4-[(phenylmethyl)amino]pyrido[4,3-d]pyrimidines: a new class of inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor // Journal of Medicinal Chemistry. 1995. Vol. 38, № 19. P. 3780–3788. DOI: https://doi.org/10.1021/jm00019a007
  4. Bansal Y., Silakari O. The therapeutic journey of benzimidazoles : a review // Bioorganic & Medicinal Chemistry. 2012. Vol. 20, № 21. P. 6208–6236. DOI: https://doi.org/10.1016/j.bmc.2012.09.013
  5. Pastor A., Alajarin R., Vaquero J. J. Synthesis and structure of new pyrido[2,3-d]pyrimidine derivatives with calcium channel antagonist activity // Tetrahedron. 1994. Vol. 50, № 27. P. 8085–8098. DOI: https://doi.org/10.1016/S0040-4020(01)85291-1
  6. Bennett L. R., Blankley C. J., Fleming R. W. Antihypertensive activity of 6-arylpyrido[2,3-d]pyrimidin-7-amine derivatives // Journal of Medicinal Chemistry. 1981. Vol. 24, № 4. P. 382–389. DOI: https://doi.org/10.1021/jm00136a006
  7. Quiroga J., Cisneros C., Insuasty B. Microwave-assisted three-component synthesis and in vitro antifungal evaluation of 6-cyano-5,8-dihydropyrido[2,3-d]pyrimidin4-(3H)-ones // Journal of Heterocyclic Chemistry. 2006. Vol. 43, № 2. P. 299–306. DOI: https://doi.org/10.1002/jhet.5570430208
  8. Ivonin M. A., Burygin G. L., Meshcheryakova A. A., Tyul’kina I. R., Sorokin V. V. Citotoksicheskaya aktivnost’ nekotoryh predstavitelej ryada benzimidazolo[1,2-a]hinazolina, pirido[1,2-a]pirimidina i pirazolokarbonitrilov [Cytotoxic activity of some representatives of a number of benzimidazolo [1,2-a] quinazoline, pyrido [1,2-a] pyrimidine and pyrazolocarbonitriles]. Mezhvuz. sb. nauch. tr. XIII Vceros. konf. molodykh uchenykh s mezhdunar. uchastiem [Interuniv. Coll. of Sci. Papers of XIII All-Russia Conf. for Young Scientists with Intern. participation]. Saratov, Saratovskiy istochnik, 2018, pp. 37–39 (in Russian).
  9.  Ivonin M. A., Dymolazova D. C., Sorokin V. V. Synthesis of orto-R-phenyl benzimidazolo-heksahydroquinazoline with angular articulation rings. Izv. Saratov Univ. (N. S.), Ser. Chemistry. Biology. Ecology, 2016, vol. 16, iss. 4, pp. 370–371. DOI: https://doi.org/10.18500/1816- 9775-2016-16-4-370-371
  10. Mosmann T. Rapid colorimetric assay for cellular growth and survival : application to proliferation and cytotoxicity assays // Journal of Immunological Methods. 1983. Vol. 65, № 1–2. P. 55–63. DOI: https://doi.org/10.1016/0022-1759(83)90303-4