title: Tandem multicomponent reactions toward the design and synthesis of novel antibacterial and cytotoxic motifs.
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 possess potent anticancer and anti bacterial 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 anti cancer 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, Klebsiellapneuomoniae, 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), andmethicillin-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.
authors: College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, UAE.
authors: Mohammad H
authors: MH
authors: Semreen
authors: Raafat
authors: R
authors: El-Awady
authors: Raed
authors: R
authors: Abu-Odeh
authors: Maha
authors: M
authors: Saber-Ayad
authors: Raed A
authors: RA
authors: Al-Qawasmeh
authors: Salem
authors: S
authors: Chouaib
authors: Wolfgang
authors: W
authors: Voelter
authors: Taleb H
authors: TH
authors: Al-Tel
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007093:Imidazoles; D011719:Pyrazines; D011725:Pyridines