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. 2022 Feb 2;27(3):1023.
doi: 10.3390/molecules27031023.

Exploring the Synergistic Anticancer Potential of Benzofuran-Oxadiazoles and Triazoles: Improved Ultrasound- and Microwave-Assisted Synthesis, Molecular Docking, Hemolytic, Thrombolytic and Anticancer Evaluation of Furan-Based Molecules

Ali Irfan  1 , Sadia Faiz  1 , Azhar Rasul  2 , Rehman Zafar  3 , Ameer Fawad Zahoor  1 , Katarzyna Kotwica-Mojzych  4 , Mariusz Mojzych  5
Affiliations

Exploring the Synergistic Anticancer Potential of Benzofuran-Oxadiazoles and Triazoles: Improved Ultrasound- and Microwave-Assisted Synthesis, Molecular Docking, Hemolytic, Thrombolytic and Anticancer Evaluation of Furan-Based Molecules

Ali Irfan et al. Molecules. .

Abstract

Ultrasound- and microwave-assisted green synthetic strategies were applied to furnish benzofuran-oxadiazole 5a-g and benzofuran-triazole 7a-h derivatives in good to excellent yields (60-96%), in comparison with conventional methods (36-80% yield). These synthesized derivatives were screened for hemolysis, thrombolysis and anticancer therapeutic potential against an A549 lung cancer cell line using an MTT assay. Derivatives 7b (0.1%) and 5e (0.5%) showed the least toxicity against RBCs. Hybrid 7f showed excellent thrombolysis activity (61.4%) when compared against reference ABTS. The highest anticancer activity was displayed by the 5d structural hybridwith cell viability 27.49 ± 1.90 and IC50 6.3 ± 0.7 μM values, which were considerably lower than the reference drug crizotinib (IC50 8.54 ± 0.84 μM). Conformational analysis revealed the spatial arrangement of compound 5d, which demonstrated its significant potency in comparison with crizotinib; therefore, scaffold 5d would be a promising anticancer agent on the basis of cytotoxicity studies, as well as in silico modeling studies.

Keywords: anticancer activities; benzofuran–oxadiazole; benzofuran–triazole; computational modeling; hemolytic activities; thrombolytic activities.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of natural and synthetic furan derivatives.
Figure 2
Figure 2
Structures of some synthetic anticancer benzofuran derivatives.
Scheme 1
Scheme 1
Synthetic pathway for microwave/ultrasound-assisted synthesis of S-alkylated oxadiazole/triazole-based benzofuran derivatives.
Figure 3
Figure 3
(A) 3D model of crizotinib with carbons (gray), oxygen (red), nitrogen (blue), fluorine (sky blue) and chlorine (green) shown; (B) 3D model of compound 5d with carbons (gray), oxygen (red), sulfur (yellow), nitrogen (blue) shown.
Figure 4
Figure 4
(a) Structure–activity relationship of hemolytic compounds 5b, 5e, 7g and 7b. (b) Structure–activity relationship of thrombolytic compounds 5a, 5g, 7f and 7h. (c) Structure–activity relationship of anticancer 5d, 5e, 7h and 7f derivatives.
Figure 5
Figure 5
(A) 3D Model of crizotinib (brown) inside the bonding pocket of protein with interactions shown; (B) 3D model of compound 5d (pink) with all atoms shown, collaborating with amino acid residues with bond distances displayed.
Figure 6
Figure 6
(A) 2D Model of crizotinib inside the bonding pocket of protein with interactions shown; (B) 2D model of compound 5d (B) with all atoms shown, collaborating with amino acid residues with bond distances displayed.
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