Synthesis, molecular modeling study, preliminary antibacterial, and antitumor evaluation of N-substituted naphthalimides
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Med Chem Res DOI 10.1007/s00044-012-0230-8
ORIGINAL RESEARCH
Synthesis, molecular modeling study, preliminary antibacterial, and antitumor evaluation of N-substituted naphthalimides and their structural analogues Adel S. El-Azab • Amer M. Alanazi • Naglaa I. Abdel-Aziz Ibrahim A. Al-Suwaidan • Magda A. A. El-Sayed • Magda A. El-Sherbeny • Alaa A.-M. Abdel-Aziz
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Received: 22 January 2012 / Accepted: 11 September 2012 Springer Science+Business Media, LLC 2012
Abstract Carboxylic acid imides 1–26 have been synthesized and screened for their antibacterial against grampositive and gram-negative organisms and their antitumor activity against 60 tumor cell lines taken from nine different organs. Compounds 12, 14, and 16 were the most active and broad-spectrum antibacterial member in this study. Compound 9 showed the most cytotoxicity with a significant inhibition for renal cancer cells. 2D-QSAR study provides details on the fine relationship linking structure and activity and offers clues for structural modifications that can improve the activity. Docking study of the compounds 12, 14, and 16 into the active site of the topoisomerase II DNA gyrase enzymes revealed a similar binding mode to bound inhibitor Clorobiocin.
A. S. El-Azab (&) A. M. Alanazi I. A. Al-Suwaidan A. A.-M. Abdel-Aziz Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia e-mail: [email protected] A. S. El-Azab Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt N. I. Abdel-Aziz M. A. El-Sherbeny A. A.-M. Abdel-Aziz (&) Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt e-mail: [email protected] M. A. A. El-Sayed Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt
Keywords Naphthalimides Cyclic imides Synthesis Antibacterial activity Antitumor evaluation Molecular modeling Modeling
Introduction Imide moiety is an integral part of structures of various important molecules such as fumaramidmycin, granulatimide, isogranulatimide, and thalidomide (Maruyama et al., 1975; Berlinck et al., 1998; Roberge et al., 1998; He´non et al., 2005; Melchert and List, 2007; Collin et al., 2001). Moreover, cyclic imides, such as succinimide, maleimide, and phthalimide possess structural features, which confer potential biological activity and pharmaceutical use (Zentz et al., 2002; Laronze et al., 2005; Amr et al., 2007; Anizon et al., 1997). The molecules contain an imide ring and the general structure –CO–N(R)–CO–, so that they are hydrophobic and neutral, and can, therefore, cross-biological membranes in vivo. Naphthalimides, one type of cyclic imides with strong hydrophobicity and desirable large pconjugated backbone, could easily interact with various active targets in biological system via non-covalent forces such as p–p stacking, and exhibit diverse biological activities including anticancer, antibacterial
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