Vilnius University, Institute of Biotechnology (Lithuania)

Vilnius University, Institute of Biotechnology (Lithuania) http://hdl.handle.net/10967/174 Fri, 27 Mar 2026 21:41:20 GMT 2026-03-27T21:41:20Z Vilnius University, Institute of Biotechnology (Lithuania) https://qsardb.org:443/repository/bitstream/id/65185d5c-7ddc-42a0-bc2c-ba1e51b190be/ http://hdl.handle.net/10967/174 Karpavičienė, I.; Valiulienė, G.; Raškevičius, V.; Lebedytė, I.; Brukštus, A.; Kairys, V.; Navakauskienė, R.; Čikotienė, I. Synthesis and antiproliferative activity of α-branched α,β-unsaturated ketones in human hematological and solid cancer cell lines. Eur. J. Med. Chem. 2015, 98, 30–48. http://hdl.handle.net/10967/178 A series of a-branched a,b-unsaturated ketones were prepared via boron trifluoride etherate mediated reaction between arylalkynes and carboxaldehydes. The evaluation of the antiproliferative activity over hematological (NB4) and solid cancer (A549, MCF-7) cell lines provided a structure-activity relationship. 5-Parameter QSAR equations were built which were able to explain 80%-92% of the variance in activity. The resulting selective lead compound showed IC50 value 0.6 mM against the hematological cell line and did not cause apoptosis, but blocked cell cycle in G0/G1. Moreover, it was demonstrated that this compound enhances and accelerates retinoic acid induced granulocytic differentiation. Tue, 01 Mar 2016 08:40:43 GMT http://hdl.handle.net/10967/178 2016-03-01T08:40:43Z Raskevicius, V.; Kairys, V. Comparison of performance of docking, LIE, metadynamics and QSAR in predicting binding affinity of benzenesulfonamides. Curr. Comput.-Aided Drug Des. 2015, 3, 237-244. http://hdl.handle.net/10967/176 The design of inhibitors specific for one relevant carbonic anhydrase isozyme is the major challenge in the new therapeutic agents development. Comparative computational chemical structure and biological activity relationship studies on a series of carbonic anhydrase II inhibitors, benzenesulfonamide derivatives, bearing pyrimidine moieties are reported in this paper using docking, Linear Interaction Energy (LIE), Metadynamics and Quantitative Structure Activity Relationship (QSAR) methods. The computed binding affinities were compared with the experimental data with the goal to explore strengths and weaknesses of various approaches applied to the investigated carbonic anhydrase/inhibitor system. From the tested methods initially only QSAR showed promising results (R2=0.83-0.89 between experimentally determined versus predicted pKd values.). Possible reasons for this performance were discussed. A modification of the LIE method was suggested which used an alternative LIE-like equation yielding significantly improved results (R2 between the experimentally determined versus the predicted ΔGbind improved from 0.24 to 0.50). Fri, 26 Feb 2016 08:01:58 GMT http://hdl.handle.net/10967/176 2016-02-26T08:01:58Z