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Synthesis, characterization, in vitro biological and molecular docking evaluation of N,N'-(ethane-1,2-diyl)bis(benzamides)

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Abstract

The present research describes the synthesis, characterization, in vitro biological and docking evaluation of N,N'-(ethane-1,2-diyl)bis(benzamides) (3a-3j). Consequently, in in vitro hRBCs hemolysis assay, only the bis-amide (3d) induced 52.4% hemolysis at higher concentration (1000 μg/mL) that decreased drastically with concentration (250 μg/mL) to 27.9% (CC50 = 400.41). Similarly, the tested bis-amide (3j) was found to be the least toxic with 7.8% hemolysis at higher concentration (1000 μg/mL) that gradually decreases to 6.1% (CC50 = 19,347.83) at lower concentration (250 μg/mL). Accordingly, the tested bis-amides were found to be highly biocompatible against hRBCs at higher concentrations with much higher CC50 values (> 1000 μg/mL). The biocompatible bis-amides (3a-3j) were subjected to in vitro DNA ladder assay to analyze their apoptotic potential. The results obtained suggest the tested bis-amides (3a-3j) are highly degradative toward DNA causing the appearance of more than one bands or complete degradation of DNA except (3a), (3c), (3i) and (3 g). Moreover, the synthesized bis-amides (3a-3j) were tested in in vitro antileishmanial assay to unveil their leishmaniacidal potential. The results obtained clearly indicated that some of the tested bis-amides displayed good dose dependent response. The tested bis-amides were highly active at higher concentration (1000 μg/mL) against the leishmanial promastigotes and their % inhibitory potential decreased drastically with concentration (250 μg/mL). Consequently, at higher concentration (1000 μg/mL), the bis-amide (3f) caused 85% inhibition and was ranked as the most effective leishmaniacidal bis-amides followed by the bis-amide (3 g) with 73.54% inhibition of leishmanial promastigotes. However, in terms of their IC50 values, the best leishmaniacidal potential was displayed by the bis-amide (3f) followed by (3b), (3j) and (3 g) with IC50 values increasing in the order of 633.16, 680.22, 680.22 and 712.93 μg/mL, respectively. Molecular docking studies revealed that bis-amides having electron-donating groups showed good binding potential against antileishmanial target.

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Acknowledgements

The author Mr. Hamid Aziz gratefully acknowledges an Indigenous scholarship from Higher Education Commission of Pakistan as a financial support for the research work performed.

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Authors and Affiliations

  1. Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Hamid Aziz & Aamer Saeed

  2. Department of Biology, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON, P3E 2C6, Canada

    Farukh Jabeen

  3. Computation, Science, Research and Development Organization, 1401, 2485 Hurontraio street, Mississauga, ON, L5A2G6, Canada

    Farukh Jabeen

  4. Department of Biotechnology, Abdul Wali Khan University, Mardan, Khyber Pukhtoonkhwa, Pakistan

    Nazif Ullah

  5. Department of Bioinformatics and Biostatistics, Shanghai Jiao Tong University, 800 Dongchuan Road,, Minhang District, Shanghai, 200240, China

    Ashfaq Ur Rehman

  6. Department of Biochemistry, Abdul Wali Khan University, Shankar Campus, Mardan, Khyber Pukhtoonkhwa, Pakistan

    Ashfaq Ur Rehman

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  1. Hamid Aziz
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  2. Aamer Saeed
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Aziz, H., Saeed, A., Jabeen, F. et al. Synthesis, characterization, in vitro biological and molecular docking evaluation of N,N'-(ethane-1,2-diyl)bis(benzamides). J IRAN CHEM SOC 18, 2425–2436 (2021). https://doi.org/10.1007/s13738-021-02199-8

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  • DOI: https://doi.org/10.1007/s13738-021-02199-8

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