Abstract
Three new 5-deoxyflavonoid and dihydroflavonoids 2, 3 and 4 have been isolated from the methanolic extract of Abutioln pakistanicum aerial parts, for which structures were elucidated explicitly by extensive MS- and NMR-experiments. In addition to these, 3,7,4′-trihydroxy-3′-methoxy flavonol (1) is reported for the first time from Abutioln pakistanicum. Compound 2 and 4 are p-coumaric acid esters while compounds 2–4 exhibited α-glucosidase inhibitory activity. Docking studies indicated that the ability of flavonoids 2, 3 and 4 to form multiple hydrogen bonds with catalytically important residues is decisive hence is responsible for the inhibition activity. The docking results signified the observed in-vitro activity quite well which is in accordance with previously obtained conclusion that phenol moiety and hydroxyl group are critical for the inhibition of α-glucosidase enzyme.
Keywords: Abutilon, Abutilon pakistanicum, 5-deoxygenated, p-coumaric acid esters, α-glucosidase, docking.
Graphical Abstract
b) Madunić, J.; Madunić, I.V.; Gajski, G.; Popić, J.; Garaj-Vrhovac, V. Apigenin: A dietary flavonoid with diverse anticancer properties. Cancer Lett., 2018, 413, 11-22.
[http://dx.doi.org/10.1016/j.canlet.2017.10.041] [PMID: 29097249]
c) Raffa, D.; Maggio, B.; Raimondi, M.V.; Plescia, F.; Daidone, G. Recent discoveries of anticancer flavonoids. Eur. J. Med. Chem., 2017, 142, 213-228.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.034] [PMID: 28793973]
[http://dx.doi.org/10.1021/np50071a032]
b) de-Melo, E.B.A. da-S. Gomesb, I. Carvalho. α- and β-glucosidase inhibitors: Chemical structure and biological activity. Tetrahedron, 2006, 62, 10277-10302.
[http://dx.doi.org/10.1016/j.tet.2006.08.055]
c) Sou, S.; Mayumi, S.; Takahashi, H.; Yamasaki, R.; Kadoya, S.; Sodeoka, M.; Hashimoto, Y. Novel alpha-glucosidase inhibitors with a tetrachlorophthalimide skeleton. Bioorg. Med. Chem. Lett., 2000, 10(10), 1081-1084.
[http://dx.doi.org/10.1016/S0960-894X(00)00161-X] [PMID: 10843222]
d) Asano, N.; Nishida, M.; Kizu, H.; Matsui, K.; Watson, A.A.; Nash, R.J. Homonojirimycin isomers and glycosides from Aglaonema treubii. J. Nat. Prod., 1997, 60, 98-101.
[http://dx.doi.org/10.1021/np960577n]
[http://dx.doi.org/10.1016/0031-9422(80)83213-4]
[http://dx.doi.org/10.1016/S0031-9422(96)00582-1]
[http://dx.doi.org/10.1248/cpb.35.611]
[http://dx.doi.org/10.3923/ajps.2003.515.518]
[http://dx.doi.org/10.1248/cpb.29.254]
b) Nonaka, G.; Kawahara, O. Tannins and related compounds. XV. A new class of dimeric flavan-3-ol gallates, theasinensins A and B, and proanthocyanidin gallates from green tea Leaf. (1). Chem. Pharm. Bull. (Tokyo), 1983, 31(11), 3706.
[http://dx.doi.org/10.1248/cpb.31.3906]
[http://dx.doi.org/10.1016/0031-9422(71)85095-1]
b) Blunder, M.; Orthaber, A.; Bauer, R.; Bucar, F.; Kunert, O. Efficient identification of flavones, flavanones and their glycosides in routine analysis via off-line combination of sensitive NMR and HPLC experiments. Food Chem., 2017, 218, 600-609.
[http://dx.doi.org/10.1016/j.foodchem.2016.09.077] [PMID: 27719955]
c) Arora, S.; Itankar, P. Extraction, isolation and identification of flavonoid from Chenopodium album aerial parts. J. Tradit. Complement. Med., 2018, 8(4), 476-482.
[http://dx.doi.org/10.1016/j.jtcme.2017.10.002] [PMID: 30302328]
[http://dx.doi.org/10.1016/0031-9422(74)85121-6]
[http://dx.doi.org/10.2116/analsci.20.1103] [PMID: 15293412]
b) Sánchez-Rabaneda, F.; Jáuregui, O.; Casals, I.; Andrés-Lacueva, C.; Izquierdo-Pulido, M.; Lamuela-Raventós, R.M. Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (Theobroma cacao). J. Mass Spectrom., 2003, 38(1), 35-42.
[http://dx.doi.org/10.1002/jms.395] [PMID: 12526004]
[http://dx.doi.org/10.1248/cpb.43.338]
[http://dx.doi.org/10.3390/70100075]
[http://dx.doi.org/10.18632/oncotarget.5215] [PMID: 26375250]
[http://dx.doi.org/10.1093/bioinformatics/bti770]
[http://dx.doi.org/10.1016/j.ejmech.2015.10.017] [PMID: 26491979]
[http://dx.doi.org/10.1016/j.ejmech.2015.01.009] [PMID: 25585009]
b) Taha, M.; Ismail, N.H.; Javaid, K.; Imran, S.; Anouar, H.; Wadood, A. Atia-Tul-Wahab; Ali, M.; Khan, K.M.; Saad, S.M.; Rahim, F.; Choudhary, M.I. Evaluation of 2-indolcarbohydrazones as potent α-glucosidase inhibitors, in silico studies and DFT based stereochemical predictions. Bioorg. Chem., 2015, 63, 24-35.
[http://dx.doi.org/10.1016/j.bioorg.2015.09.001] [PMID: 26398141]
c) Taha, M.; Ismail, N.H.; Imran, S.; Wadood, A.; Rahim, F.; Ali, M.; Rehman, A.U. Novel quinoline derivatives as potent in vitro α-glucosidase inhibitors: in silico studies and SAR predictions. MedChemComm, 2015, 6, 1826-1836.
[http://dx.doi.org/10.1039/C5MD00280J]
[http://dx.doi.org/10.1016/j.bmc.2015.06.060]
[http://dx.doi.org/10.1002/(SICI)1096-987X(199604)17:5/6<587:AID-JCC4>3.0.CO;2-Q]
[http://dx.doi.org/10.1002/jms.585] [PMID: 14760608]