Biological Potential of Novel Methoxy and Hydroxy Substituted Heteroaromatic Amides Designed as Promising Antioxidative Agents: Synthesis, 3D-QSAR Analysis, and Biological Activity [component]

unpublished
This paper discusses antioxidative and biological activity of 25 novel amidino substituted benzamides with a variety of heteroaromatic nuclei attached to the benzamide moiety and with a variable number of methoxy and/or hydroxy substituents. Targeted compounds, bearing either amidino or 2-imidazolinyl substituent, were obtained in the Pinner reaction from cyano precursors. 3D-QSAR models were generated to predict antioxidative activity of the 25 novel aromatic and heteroaromatic benzamide
more » ... tives. The compounds were tested for antioxidative activity using in vitro spectrophotometric assays. Direct validation of 3D-QSAR approach for predicting activities of novel benzamide derivatives was carried out by comparing experimental and computationally predicted antioxidative activity. Experimentally determined activities for all novel compounds were found to be within standard deviation of error of the models. Following this, structure-activity relationships among the synthesized compounds are discussed. Furthermore, antiproliferative activity in vitro against HeLa cells as well as antibacterial and antifungal activity was tested to confirm the other biological activities of the prepared compounds. antiproliferative activity in vitro, antimicrobial activity trichloride or boron tribromide in absolute dichloromethane at -75 °C. Reaction yields of all compounds were moderate. By using boron trichloride, only one methoxy group has been removed from the compounds 5, 21 and 24 which allowed the synthesis of compounds 8, 27 and 29 with one methoxy and one hydroxy group. 2D NOESY NMR spectra confirmed that the methoxy group at the position 2 (R1) was successfully deprotected. Target compounds with variable number of hydroxy 11-17 and 30-37 and/or methoxy groups 38-47 bearing amidino or 2-imidazolinyl substituent were prepared in acidic twostep Pinner reaction from corresponding cyano precursors due to reaction with NH3(g) or ethylenediamine (EDA). Scheme 2. The progress of the reaction was monitored by IR spectroscopy. In order to ensure their better water solubility, all amidino substituted derivatives were prepared as hydrochloride salts. Due
doi:10.1021/acs.chemrestox.9b00256.s001 fatcat:vtionxevrbg5rch7eyswhac3va