Med Chem Res DOI 10.1007/s00044-017-2080-x MEDICINAL CHEMISTR Y RESEARCH ORIGINAL RESEARCH In vitro anticholinesterase activity and molecular docking studies of coumarin derivatives isolated from roots of Heptaptera cilicica Hilal Özbek 1 ● Zühal Güvenalp 1 ● Gülderen Yılmaz 2 ● Kadir Ö. Yerdelen 3 ● Cavit Kazaz 4 ● Ömür L. Demirezer 5 Received: 17 July 2016 / Accepted: 15 September 2017 © Springer Science+Business Media, LLC 2017 Abstract The chloroform extract of the roots of Heptaptera cilicica (Boiss. & Bal.) Tutin (Apiaceae) was investigated in terms of acetylcholinesterase (AChE) and butyr- ylcholinesterase (BuChE) inhibitory effects by Ellman method. Afterwards, a new furocoumarin: trichoclin ange- late with five known coumarin derivatives: umbelliprenin, badrakemone, badrakemin, badrakemin acetate and prunate were isolated from this extract. Their structures were iden- tified by means of spectroscopic methods (1D, 2D-NMR and HRESIMS). The next step of our study was determin- ing AChE and BuChE inhibitory activities of the com- pounds by molecular docking and in vitro methods. According to the results, prunate was found to be the most potent compound, which exhibited significant inhibitory potency against acetylcholinesterase (IC 50 = 1.76 ± 0.003 μM) and butyrylcholinesterase (IC 50 = 0.21 ± 0.002 μM) as compared with the reference compound, galantamine hydrobromide. Keywords Heptaptera cilicica ● Apiaceae ● Coumarin ● AChE ● BuChE Introduction Alzheimer’s disease is a neurodegenerative disorder that characterized by progressive loss of cognitive functions (Moreira et al. 2017). Plants contain active compounds have become new sources to investigate for the pharmaceutical industry. Numerous plants have been used to treat neuro- degenerative diseases (Adewusi et al. 2010). Heptaptera (Apiaceae) is represented with four species in Turkey (Herrnstadt and Heyn 1972). These species are known to be rich in coumarin derivatives (Appendino et al. 1993, 1992a, 1992b). Several coumarins have showed inhibition against acetylcholinesterase (AChE). AChE inhibitory effect of Heptaptera cilicica root extract has been stated as more effective than fruit and aerial part extracts in a previous study. This led us to study on root extract to yield active coumarins (Şenol et al. 2010). In a continuation of the previous research, in vitro butyrylcholinesterase (BuChE) inhibitory activity was stu- died in addition to AChE inhibitory activity of Heptaptera cilicica root extract by Ellman method. Afterwards cou- marin derivatives were isolated from chloroform extract. Finally, AChE and BuChE inhibitory activities of the sec- ondary metabolites were evaluated by molecular docking studies and in vitro Ellman method. * Zühal Güvenalp guvenalp@atauni.edu.tr 1 Department of Pharmacognosy, Faculty of Pharmacy, Atatürk University, 25240 Erzurum, Turkey 2 Department of Pharmaceutical Botany, Faculty of Pharmacy, Ankara University, 06100 Ankara Turkey 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Atatürk University, 25240 Erzurum Turkey 4 Department of Chemistry, Faculty of Science, Atatürk University, 25240 Erzurum, Turkey 5 Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey