Exploring Antiproliferative Activity of Heteroaromatic Amides and Their Fused Derivatives

Exploring antiproliferative activity of heteroaromatic amides and their fused derivatives using 3D-QSAR, synthesis and biological tests

Irena Sović[a], Marko Viskić[a], Branimir Bertoša[b]*, Katja Ester[c], Marijeta Kralj[c], Marijana Hranjec[a]*and Grace Karminski-Zamola[a]

[a] Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P. O. Box 177, HR-10000 Zagreb, Croatia;

[b] Department of Physical Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia

[c] Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, P. O. Box 180, HR-10000 Zagreb, Croatia;

* Corresponding authors: Dr. Marijana Hranjec, Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, P. O. Box 177, HR-10000 Zagreb, Croatia, Phone No. +38514597245; Fax No. ++38514597250; e-mail: ; Dr. Branimir Bertoša, Department of Physical Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR-10000 Zagreb, Croatia, Phone No. +38514561025; Fax No. +38514680245; e-mail: .

Contents of Supporting Information:

1.  Figures S1-S7 related to QSAR results.

Figure S1. Predicted vs. experimental antitumor activity of model 1A.

Figure S2. Predicted vs. experimental antitumor activity of model 1B.

Figure S3. Predicted vs. experimental antitumor activity of model 1C.

Figure S4. Products of the descriptor’s average value (calculated for the dataset used to built the model) and the associated PLS coefficient in case ofmodel 1A-e, B). Descriptors with the highest impact on the activity are labelled; list and description of all 128 VolSurf+ descriptors is given in the VolSurf+ manual.27

Figure S5. Products of the descriptor’s average value (calculated for the dataset used to built the model) and the associated PLS coefficient in case of model 1B-e. Descriptors with the highest impact on the activity are labelled; list and description of all 128 VolSurf+ descriptors is given in the VolSurf+ manual.[27]

Figure S6. Products of the descriptor’s average value (calculated for the dataset used to built the model) and the associated PLS coefficient in case of model 1C-e. Descriptors with the highest impact on the activity are labelled; list and description of all 128 VolSurf+ descriptors is given in the VolSurf+ manual.[27]

Figure S7. PCA scores plot. Descriptors with the highest contribution to the first two PCs are labeled: W1–W3 (hydrophilic regions), WO1 (H-bond donor descriptor, calculated with carbonyl oxygen as the probe), WN1 (H-bond acceptor descriptor, calculated with neutral amide group as the probe), V (volume), S (surface) and HSA (the sum of hydrophobic surface areas). List and description of all 128 descriptors is given in the VolSurf+ manual.[27]

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