Background: Cancer is a major health problem acting as a global killer and one of the leading
causes of death. Most cancer chemotherapeutic drugs currently in clinical use are to kill malignant
tumour cells by inhibiting some of the mechanisms implied in cellular division. Thienopyrimidines occupy
a special position among the fused pyrimidines, along with other pyrimidines containing an annelated
five membered hetero aromatic ring; forms a significant class of drugs which exhibit an array of
various biological activities. One of the important current anticancer agent gefitinib acts as tyrosine
kinase inhibitors is a quinazoline derivative. The thieno[2,3-d]pyrimidine ring system, is considered as a
bioisostere of quinazoline moiety and have attracted great attention due to their broad bioactivities, including
Methods: Novel thienopyrimidine derivatives were synthesized by cyclization of thiophene o-amino
esters with lactam salts such as pyrrolidin-2-one, piperidin-2-one and caprolactam by treating using
phosphorous oxychloride. The next set of compounds thieno[2,3-d]pyrimidin-4(3H)-one were synthesised
by Niementowski condensations between 2-aminothiophene carboxylate and formamide under
reflux condition, followed by its chlorination in good yield. Microwave Fusion of 4-chlorothieno[2,3-d]
pyrimidines with o-phenylenediamine afforded target compounds. The target compounds were tested on
MCF-7 and HEK293 cell line.
Results: The synthesized thirty compounds structures were established by IR, 1H NMR and Mass spectroscopy.
The synthesized compounds were obtained in the good yield ranging from 45-70%. The synthesized
compounds were subjected to cytotoxicity studies. Among the twenty compounds only one
compound showed moderate activity. One of the compound 2c bearing acetyl group had IC50 48.93 μM.
However decrease in the size of the lactam ring from six to five member ring or increase to seven member
ring resulted in the loss of activity. The IC50 value of 5a was found to be 70.86μg/ml. The compound
5i have more cytotoxic action among the series.
Conclusion: A series of thirty compounds belonging to novel pyyrolo, pyrido and benzimidazole fused
thienopyrimidines were synthesized, characterized and were evaluated for their in vitro cytotoxicity.
The compounds bearing bulky group such as terbutyl group and chloro substitution had the best activity.
In conclusion, these structures seems to have biological properties and further investigation on this
group could provide a lead.