Benzopyrazines: Synthesis, Characterization and Evaluation as Aldose Reductase Inhibitors
Science Journal of Chemistry
Volume 7, Issue 5, October 2019, Pages: 90-97
Received: Sep. 14, 2019; Accepted: Oct. 15, 2019; Published: Oct. 24, 2019
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Huma Aslam Bhatti, Hussian Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
Qurat-Ul-Ain Zaheer, Hussian Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
Yildiz Tehseen, Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, Pakistan
Zahid Shaiq, Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, Pakistan
Khalid Mohammed Khan, Hussian Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
Abdul Hameed, Hussian Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
Jamshed Iqbal, Hussian Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
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Role of aldose reductase (ALR2) in diabetic complications such as retinopathy, nephropathy, neuropathy, and cataract etc. is well-evident. ALR2 in the first step of polyol pathway reduces glucose to sorbitol whose elevated level leads to diabetic cataract, characterize by clouding of the lens in the eye that affects vision. Inhibition of ALR2 enzyme with small molecules as inhibitor is a rapid approach for diabetic management. In the present study the synthetic route to synthesize desired benzopyrazines and a library of sixteen (16) methyl benzopyrazines were screened against aldose reductase. From the bioactivity results, the 3'-hydroxyphenyl benzopyrazine 6l was found most active (IC50 = 1.34 ± 0.07 µM) while 3'-bromophenyl analogue 6i showed comparable activity for ALR2 (IC50 = 3.48 ± 0.66 µM) as compared to standard sorbinil (IC50 = 3.14 ± 0.02 µM). Both compounds (6l and 6i) showed excellent selectivity for ALR2 over aldehyde reductase (ALR1) which has important role in detoxification of toxic aldehydes. The structure of two regio-isomers were fully characterize by 1H and 13C NMR two dimensional NMR techniques including COSY, NOESY, HSQC, and HMBC. Regio-isomers separation was proved to be difficult in different solvent systems. Only an isomer of 3'-bromo benzopyrazine 6i' was isolated that help to assign the structure of regioisomers from NMR data. All the benzopyrazines were fully characterized by using different spectral techniques including 1H, 13C NMR, IR spectroscopy, and mass spectrometry.
Aldose Reductase, Polyol Pathway, Aldehyde Reductase, Benzopyrazines, Diabetic Complications
To cite this article
Huma Aslam Bhatti, Qurat-Ul-Ain Zaheer, Yildiz Tehseen, Zahid Shaiq, Khalid Mohammed Khan, Abdul Hameed, Jamshed Iqbal, Benzopyrazines: Synthesis, Characterization and Evaluation as Aldose Reductase Inhibitors, Science Journal of Chemistry. Special Issue: Benzopyrazines: Synthesis, Characterization and Evaluation as Aldose Reductase Inhibitors. Vol. 7, No. 5, 2019, pp. 90-97. doi: 10.11648/j.sjc.20190705.11
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