Muhammad Shabbir

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.

Synthesis, Characterization, and Pharmacological Evaluation of Selected Aromatic Amines

Aromatic amines 1-amino-4-phenoxybenzene (A-1A), 2-(4-aminophenoxy) naphthalene (A-2A), and 1-(4-aminophenoxy) naphthalene (A-3A) were synthesized by the reduction of corresponding nitroaromatics with hydrazine monohydrate and Pd/C 5% (w/w). The newly synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, UV-visible spectrophotometer, and mass spectrometry and their biological activities were investigated along with structurally similar 4-(4-aminophenyloxy) biphenyl (A-A). Results of brine shrimp cytotoxicity assay showed that almost all of the compounds had LD50 values <1 μg/mL. The compounds also showed significant antitumor activity with IC50 values ranging from 67.45 to 12.2 µgmL−1. The cytotoxicity and antitumor studies correlate the results which suggests the anticancerous nature of compounds. During the interaction study of these compounds with DNA, all of the compounds showed hyperchromic effect indicating strong interaction through binding with the grooves of DNA. Moreover, A-3A also showed decrease in confirming higher propensity for DNA groove binding. In DPPH free radical scavenging assay, all the compounds showed potential antioxidant capability. The compounds were highly active in protecting DNA against hydroxyl free radicals. DNA interaction and antioxidant results back up each other indicating that these compounds have potential to be used as cancer chemopreventive agents. Additionally, one compound (A-1A) showed significant antibacterial and antifungal activity as well.

Synthesis, characterization and biological properties of novel ON donor bidentate Schiff bases and their copper(II) complexes

Abstract Four novel ON donor Schiff bases (E)-3-((4-phenoxyphenylimino)methyl)benzene-1,2-diol (HL1),(E)-3-((4-(4-biphenyloxy)phenyliminomethyl)benzene-1,2-diol (HL2), (E)-3-((4-naphthoxyphenylimino)methyl)benzene-1,2-diol (HL3), (E)-3-((4-(2-naphthoxy)phenylimino)methyl)benzene-1,2-diol (HL4) and their copper(II) complexes bis((E)-3-((4-phenoxyphenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L1)2) bis((E)-3-((4-(4-biphenyloxy)phenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L2)2), bis((E)-3-((4-naphthoxyphenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L3)2), bis((E)-3-((4-(2-naphthoxy)phenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L4)2) have been synthesized and characterized by spectroscopic (FTIR, NMR, UV–visible) and elemental analysis. The crystal structures of HL1, HL2, HL3, and HL4 have been determined, which reveal intramolecular N-H⋯O (HL1, HL2, HL3, and HL4) hydrogen bonds in the solid state. Keto-amine and enol-imine tautomerism is exhibited by the Schiff bases in solid and solution states. The Schiff bases and their copper(II) complexes have been screened for their biological activities. In antimicrobial assays (antibacterial and antifungal), HL4 showed promising results against all strains through dual inhibition property while the rest of the compounds showed activity against selective strains. On the other hand, in cytotoxic, DPPH, and inhibition of hydroxyl (OH) free radical-induced DNA damage assays, the results were found significantly correlated with each other, i.e. the ligands HL1 and HL2 showed moderate activity while their complexes Cu(L1)2 and Cu(L2)2 exhibited prominent increase in activity. As the results of these assays are supporting each other, it represents the strong positive correlation and antioxidant nature of investigated compounds.

Synthesis and bioelectrochemical behavior of aromatic amines

Four aromatic amines 1-amino-4-phenoxybenzene (A1), 4-(4-aminophenyloxy) biphenyl (A2), 1-(4-aminophenoxy) naphthalene (A3) and 2-(4-aminophenoxy) naphthalene (A4) were synthesized and characterized by elemental, spectroscopic (FTIR, NMR), mass spectrometric and single crystal X-ray diffraction methods. The compounds crystallized in monoclinic crystal system with space group P21. Intermolecular hydrogen bonds were observed between the amine group and amine/ether acceptors of neighboring molecules. Electrochemical investigations were done using cyclic voltammetry (CV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV). CV studies showed that oxidation of aromatic amines takes place at about 0.9 V (vs. Ag/AgCl) and the electron transfer (ET) process has irreversible nature. After first scan reactive intermediate were generated electrochemically and some other cathodic and anodic peaks also appeared in the succeeding scans. DPV study revealed that ET process is accompanied by one electron. DNA binding study of aromatic amines was performed by CV and UV-visible spectroscopy. These investigations revealed groove binding mode of interaction of aromatic amines with DNA.