Tandem Multicomponent Reactions Toward the Design and Synthesis of Novel Antibacterial and Cytotoxic Motifs

Mohammad   H.   Semreen; Raafat      El-Awady; Raed      Abu-Odeh; Maha      Saber-Ayad; Raed   A.   Al-Qawasmeh; Salem      Chouaib; Wolfgang      Voelter; Taleb   H.   Al-Tel

doi:10.2174/0929867311320110007

Abstract

The synthesis of polysubstituted imidazopyridines and imidazopyrazines through the orthogonal union of Groebke-Blackburn and Ugi reactions is described. These motifs were produced efficiently in a tandem operation without intermediate isolation. The synthesized scaffolds were biologically evaluated and found to posses potent anticancer and antibacterial activities. Importantly, some of these motifs (e.g. compound 5) were found to possess specific anti-breast cancer activity against MCF7 cell line and others (e.g. compound 15) possess specific effects against melanoma cancer cell line (M8). Interestingly, the introduction of imidazobenzothiazole framework produced compounds with potent anticancer activities (e.g. compounds 29 and 33) in vitro. Interestingly, many of synthesized compounds displayed potent and broad spectrum antibacterial activity against hospital-resistant clinical isolates namely, Escherichia coli, Klebsiella pneuomoniae, Staph. epidermidis, Ps. aeruginosa and Proteus vulgaris. Furthermore, many of the synthesized motifs were found to effective against Gram positive methicillin-sensitive Staphylococcus aureus (MMSA; ATCC 25923), and methicillin-resistant Staphylococcus aureus (MRSA; ATCC 35591). These findings, however, form the foundation for further investigation in our continuing efforts to develop selective anticancer and antibacterial agents.

Keywords: Imidazopyridines, Ugi reaction, multicomponent reaction, Groebke-Blackburn reaction, antibacterial, hospital resistant strains, anticancer.

« Previous