Computationally guided search for novel benzimidazole derivatives with enhanced antiproliferative activity (CROSBI ID 678215)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Bertoša, Branimir ; Vušak, Darko ; Perin, Nataša ; Martin-Kleiner, Irena ; Kralj, Marijeta ; Karminski-Zamola, Grace ; Hranjec, Marijana
engleski
Computationally guided search for novel benzimidazole derivatives with enhanced antiproliferative activity
The experimental search for novel benzimidazole derivatives with enhanced antiproliferative activity was successfully guided by QSAR modelling. Robust 3D-QSAR models were derived using available database of the compounds with previously measured activities in the same laboratory, under the same conditions. Using the QSAR analysis of the obtained models, the molecular descriptors with the highest influence on the activity were identified. The QSAR analysis revealed that the antiproliferative activities against four cell lines, H460, HCT 116, MCF-7, and SW 620, should be increased if the new compounds are charged at pH range from 5 to 7 and if their hydrophobicity is increased comparing to the dataset compounds. Novel amino and diamino substituted benzimidazo[1, 2-a]quinolines with introduced quarter amino groups and aliphatic chains were designed according to the QSAR analysis and their antiproliferative activities were computationally predicted. Using uncatalyzed microwave assisted amination, 14 novel compounds were synthesized and their antiproliferative activities were assessed against H460, HCT 116, MCF-7, and SW 620 tumor cell lines in vitro. Novel compounds showed antiproliferative activities in micromolar and submicromolar inhibition concentrations. Experimental measurements of antiproliferative activities enabled undisputed validation of QSAR models, very good agreement between experimentally measured activities and computational predictions was obtained. Based on the identified molecular descriptors with the highest influence on antiproliferative activity, possible mode of action is proposed.
QSAR ; benzimidazole derivatives ; antiproliferative activity
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Podaci o prilogu
109-109.
2017.
objavljeno
Podaci o matičnoj publikaciji
25. Hrvatski skup kemičara i kemijskih inženjera s međunarodnim sudjelovanjem ; 3. simpozij Vladimir Prelog : knjiga sažetaka = 25th Croatian Meeting of Chemist and Chemical Engineers with international participation. 3rd symposium “Vladimir Prelog” : Book of Abstracts
Šantić, Ana ; Đaković, Marijana
Zagreb: Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI) ; Hrvatsko kemijsko drustvo
978-953-552327-7
Podaci o skupu
25. Hrvatski skup kemičara i kemijskih inženjera s međunarodnim sudjelovanjem ; 3. simpozij Vladimir Prelog = 25th Croatian Meeting of Chemist and Chemical Engineers with international participation. 3rd symposium “Vladimir Prelog”
poster
12.04.2017-22.04.2017
Poreč, Hrvatska