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Research Paper

Synthesis, anticancer evaluation and molecular docking studies of new benzimidazole- 1,3,4-oxadiazole derivatives as human topoisomerase types I poison

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Pages 1657-1673 | Received 17 May 2020, Accepted 28 Jul 2020, Published online: 19 Aug 2020

Figures & data

Figure 1. Hoechst 33258 and Hoechst 33342 compounds.

Figure 1. Hoechst 33258 and Hoechst 33342 compounds.

Table 1. Hydrogen and carbon values of compound 5e detected by 2 D NMR.

Table 2. IC50 values (µM) of the compounds 5a-5o, doxorubicin and Hoechst 33342 against A549, MCF-7, C6, HepG2, HeLa and NIH3T3.

Figure 2. % DNA synthesis inhibition activities of compound 5n and doxorubicin against A549 cell line.

Figure 2. % DNA synthesis inhibition activities of compound 5n and doxorubicin against A549 cell line.

Figure 3. % DNA synthesis inhibition activities of compounds 5a, 5d, 5e, 5o and doxorubicin against MCF-7 cell line.

Figure 3. % DNA synthesis inhibition activities of compounds 5a, 5d, 5e, 5o and doxorubicin against MCF-7 cell line.

Figure 4. % DNA synthesis inhibition activities of compound 5a and doxorubicin against HepG2 cell line.

Figure 4. % DNA synthesis inhibition activities of compound 5a and doxorubicin against HepG2 cell line.

Figure 5. % DNA synthesis inhibition activities of compound 5k and doxorubicin against C6 cell line.

Figure 5. % DNA synthesis inhibition activities of compound 5k and doxorubicin against C6 cell line.

Figure 6. % DNA synthesis inhibition activities of compounds 5 b, 5 l, 5n and doxorubicin against HeLa cell line.

Figure 6. % DNA synthesis inhibition activities of compounds 5 b, 5 l, 5n and doxorubicin against HeLa cell line.

Figure 7. The flow cytometric analysis diagram of compound 5n and doxorubicin for A549 cell line.

Figure 7. The flow cytometric analysis diagram of compound 5n and doxorubicin for A549 cell line.

Figure 8. The flow cytometric analysis diagram of compounds 5d, 5e, 5o and doxorubicin for MCF-7 cell line.

Figure 8. The flow cytometric analysis diagram of compounds 5d, 5e, 5o and doxorubicin for MCF-7 cell line.

Figure 9. The flow cytometric analysis diagram of compound 5k and doxorubicin for C6 cell line.

Figure 9. The flow cytometric analysis diagram of compound 5k and doxorubicin for C6 cell line.

Figure 10. The flow cytometric analysis diagram of compound 5a and doxorubicin for HepG2 cell line.

Figure 10. The flow cytometric analysis diagram of compound 5a and doxorubicin for HepG2 cell line.

Figure 11. The flow cytometric analysis diagram of compounds 5 b, 5 l, 5n and doxorubicin for HeLa cell line.

Figure 11. The flow cytometric analysis diagram of compounds 5 b, 5 l, 5n and doxorubicin for HeLa cell line.

Figure 12. Topo I activity of compounds 5a, 5 b, 5d, 5e, 5k, 5 l, 5n, 5o, Hoechst 33342 and camptothecin.

Figure 12. Topo I activity of compounds 5a, 5 b, 5d, 5e, 5k, 5 l, 5n, 5o, Hoechst 33342 and camptothecin.

Figure 13. Three-dimensional interaction of Hoechst 33342 with the DNA-Topoisomerase I enzyme complex active site.

Figure 13. Three-dimensional interaction of Hoechst 33342 with the DNA-Topoisomerase I enzyme complex active site.

Figure 14. Docking poses of compound 5n. (A) Placement of the compound 5n on the DNA-Topoisomerase I enzyme complex active site. (B) The interacting mode of compound 5n in the active region of DNA-Topoisomerase I enzyme. (C) Van der Waals interaction of DNA-Topoisomerase I enzyme complex active site of compound 5n. (D) Electrostatic interaction of DNA-Topoisomerase I enzyme complex active site of compound 5n.

Figure 14. Docking poses of compound 5n. (A) Placement of the compound 5n on the DNA-Topoisomerase I enzyme complex active site. (B) The interacting mode of compound 5n in the active region of DNA-Topoisomerase I enzyme. (C) Van der Waals interaction of DNA-Topoisomerase I enzyme complex active site of compound 5n. (D) Electrostatic interaction of DNA-Topoisomerase I enzyme complex active site of compound 5n.

Scheme 1. Continued.

Scheme 1. Continued.

Table 3. Binding affinity and interacting residues of compound 5n and Hoechst.

Supplemental material

Supplemental Material

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