Synthesis and antitumor activity of heterocycles related to carbendazim

William A. Remers, Bhashyam S. Iyengar, Robert T Dorr, Lee Wisner, Robert B. Bates

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Three types of compounds were synthesized from carbendazim (1), a benzimidazole derivative (Scheme 1). They included a group of esters at N1 prepared by treating carbendazim with isocyanates bearing ester groups (2a-2c), carboxyalkyl-1,2,3,4-tetrahydro-s-triazino[1,2-a]benzimidazole-2,4-dione esters (3a and 3d) formed by cyclization of two of these esters, and related hydrophilic amides 3b and 3c derived from 3a. The antitumor potencies of the N1 esters were in the range of 7 to 40 mM, which compares favorably with carbendazim, but their water solubilities were low. The s-triazine derivatives showed activity against pancreatic tumor cells, and one of them (3b) was active in mice, but they were not effective against other tumor types. Treatment of carbendazim with 3-bromopropionyl chloride produced 1-methoxycarbonyl- 4-oxo-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole (4), which gave 1-(3-aminopropionyl)benzimidazole 2-methylcarbamates, substituted on the amino nitrogen (5a, 5b, and 5d), when treated with amines. These products showed some antitumor activity in cell cultures, and an ethoxy derivative (5c), obtained by treating 1-methoxycarbonyl-4-oxo-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole with sodium ethoxide, was active in the 67-150 mM range. Some of the new compounds had good water solubility. Carbendazim kills tumor cells by inhibiting tubulin; however, s-triazine 3b, which differs from it in size and functional groups, does not act by this mechanism.

Original languageEnglish (US)
Pages (from-to)136-141
Number of pages6
JournalJournal of Heterocyclic Chemistry
Volume52
Issue number1
DOIs
StatePublished - 2015

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Esters
Tumors
Triazines
Derivatives
Bearings (structural)
Solubility
Cells
Isocyanates
Water
Cyclization
Tubulin
Cell culture
Amides
Functional groups
Amines
Chlorides
Nitrogen
benzimidazole
carbendazim

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis and antitumor activity of heterocycles related to carbendazim. / Remers, William A.; Iyengar, Bhashyam S.; Dorr, Robert T; Wisner, Lee; Bates, Robert B.

In: Journal of Heterocyclic Chemistry, Vol. 52, No. 1, 2015, p. 136-141.

Research output: Contribution to journalArticle

Remers, William A. ; Iyengar, Bhashyam S. ; Dorr, Robert T ; Wisner, Lee ; Bates, Robert B. / Synthesis and antitumor activity of heterocycles related to carbendazim. In: Journal of Heterocyclic Chemistry. 2015 ; Vol. 52, No. 1. pp. 136-141.
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