Abstract
Background: Diabetes is the primary cause of fatality and disability all over the world, in recent past, we have reported various classes of compounds as anti-glycating agents and we have also reported benzimidazole and benzothiazole derivatives as a potential class of anti-glycating agents. This encouraged us to evaluate the pyridinyl benzimidazole/pyridinyl benzothiazole derivatives 1-27 for yeast glucose uptake activity.
Methods: In the present study, an equimolar mixture of pyridine carboxaldehyde derivatives (1 mmol) and sodium metabisulphite (1 mmol) in DMF (10 mL) was stirred for 10 to 15 min, followed by addition of o-phenylene diamine/2-aminothiophenol (1 mmol) into it and refluxed for 3 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into crushed ice. Precipitates were formed which were collected by filtration to produce compounds 1-27 in good yields. Recrystallization from methanol yielded pure crystals.
Results: Our present study showed that all compounds showed a varying degree of yeast glucose uptake activity in the range IC50 = 36.43-272.20 µM, compared to standard metronidazole (IC50 = 41.86 ± 0.09 µM). Compounds 5 (IC50 = 38.14 ± 0.17 µM), 6 (IC50 = 40.23 ± 0.20 µM), and 7 (IC50 = 36.43 ± 0.02 µM) showed an excellent yeast glucose uptake activity better than the standard.
Conclusion: Pyridinyl benzimidazole/pyridinyl benzothiazole derivatives 1-27 were synthesized, structurally characterized, and evaluated for in vitro yeast glucose uptake activity. Compounds 5 (IC50 = 38.14 ± 0.17 µM), 6 (IC50 = 40.23 ± 0.20 µM), and 7 (IC50 = 36.43 ± 0.02 µM) demonstrated potent yeast glucose uptake activity as compared to standard metronidazole (IC50 = 41.86 ± 0.09 µM). This study identified a number of potential lead molecules which can be helpful in lowering the blood glucose level in hyperglycemia.
Keywords: Pyridinyl benzimidazole, benzothiazole, yeast glucose uptake, in vitro, structure-activity relationship, hyperglycemia.
Graphical Abstract
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(b)Abbasi, S.; Mirza, S.; Rasheed, S.; Hussain, S.; Khan, J.A.J.; Khan, K.M.; Perveen, S.; Choudhary, M.I. Benzothiazole derivatives: Novel inhibitors of methylglyoxal mediated glycation of protein in vitro. Med. Chem., 2014, 10, 824.
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(g)Khan, K.M.; Khan, M.; Ali, M.; Taha, M.; Rasheed, S.; Perveen, S.; Choudhary, M.I. Synthesis of bis-Schiff bases of isatins and their antiglycation activity. Bioorg. Med. Chem., 2009, 17, 7795.
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(i)Khan, K.M.; Mughal, U.R.; Ambreen, N.; Khan, A.; Perveen, S.; Choudhary, M.I. Schiff bases of istain: Antiglycation activity. Lett. Drug Des. Discov., 2009, 6, 358.
(j)Khan, K.M.; Khan, M.; Ambreen, N.; Taha, M.; Rahim, F.; Rasheed, S.; Saied, S.; Safi, H.; Perveen, S.; Choudhary, M.I. Oxindole derivatives: Synthesis and antiglycation activity. Med. Chem., 2013, 9, 681.
(k)Perveen, S.; Mustafa, S.; Khan, K.M.; Choudhary, M.I. 1,3-Disubstituted ureas as antiglycating agents. J. Chem. Soc. Pak., 2013, 35, 1603.
(l)Khan, K.M.; Saeed, S.; Ali, M.; Gohar, M.; Zahid, J.; Khan, A.; Perveen, S.; Choudhary, M.I. Unsymmetrically disubstituted urea derivatives: A potent class of antiglycating agents. Bioorg. Med. Chem., 2009, 17, 2447.
(m)Taha, M.; Ismail, N.H.; Jamil, W.; Rashwan, H.; Kashif, S.M.; Sain, A.A.; Adenan, M.I.; Anouar, E.H.; Rahim, F.; Khan, K.M. Synthesis of novel derivatives of 4-methylbenzimidazole and evaluation of their biological activities. Eur. J. Med. Chem., 2014, 84, 731.
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