Synthesis, biological and electrochemical evaluation of novel nitroaromatics as potential anticancerous drugs.
Nitroaromatics i.e. 1-nitro-4-phenoxybenzene (1), 4-(4-nitrophenyloxy) biphenyl (2), 1-(4-nitrophenoxy) naphthalene (3) and 2-(4-nitrophenoxy) naphthalene (4) were synthesized by Williamson etherification and characterized by elemental analysis, FTIR, NMR ((1)H, (13)C), UV-visible spectroscopy, mass spectrometry and single crystal X-ray diffraction analysis. Their brine shrimp cytotoxicity resulted in LD50 values <1 μg/mL indicating significant antitumor activity with IC50 values ranging from 29.0 to 8.4 μg/mL. They are highly active in protecting DNA against hydroxyl free radicals in a concentration dependent manner. Voltammetric studies showed one electron reversible reduction at a platinum electrode with diffusion coefficient (Do) values of the order ~10(-6)-10(-7) cm(2)s(-1). Strong interaction with the human blood DNA through intercalative mode was contemplated through electrochemical and UV-visible spectroscopic studies which are in agreement with the conclusions drawn from biological analysis, unravelling the potential anticancerous nature of the synthesized compounds.
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Muhammad
M
Shabbir
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: zareenakhter@yahoo.com.
Zareen
Z
Akhter
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan; Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan.
Iqbal
I
Ahmad
Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Safeer
S
Ahmed
Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Hammad
H
Ismail
Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
Bushra
B
Mirza
Chemistry Department Loughborough University, Loughborough LE113TU, UK.
Vickie
V
Mckee
Institutfür Anorganische Chemie, J.W. Goethe-Universität Frankfurt, Max-Von-Laue-Strasse 7, Frankfurt/Main 60438, Germany.
Michael
M
Bolte
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001156:Artemia; D060326:Chemistry Techniques, Synthetic; D004247:DNA / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004563:Electrochemistry; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000737:chemistry; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D009574:Nitro Compounds; D017665:Hydroxyl Radical; D004247:DNA
Drug–DNA intercalation; Nitroaromatics; Reversible electron transfer