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. 2023 Jun 28;13(28):19530-19539.
doi: 10.1039/d3ra02690f. eCollection 2023 Jun 22.

Artemisia herba-alba sesquiterpenes: in silico inhibition in the ATP-binding pocket

Tarik A Mohamed  1 , Mohamed H Abd El-Razek  2 , Ibrahim A Saleh  1 , Sherin K Ali  1 , Abeer A Abd El Aty  3 , Paul W Paré  4 , Mohamed-Elamir F Hegazy  1
Affiliations

Artemisia herba-alba sesquiterpenes: in silico inhibition in the ATP-binding pocket

Tarik A Mohamed et al. RSC Adv. .

Abstract

To identify antimicrobial leads for medical applications, metabolites from the aerial part of Artemisia herba-alba were extracted and chromatographically purified. Two new sesquiterpenes, 1β,8α-dihydroxyeudesm-4-en-6β,7α,11βH-12,6-olide (1) and 1β,6α,8α-trihydroxy, 11α-methyl-eudesma-4(15)-en-13-propanoate (2) along with a known eudesmanolide 11-epi-artapshin (3) were identified. Structures were determined by spectroscopic methods including 1D- and 2D-NMR as well as mass spectroscopy. Compound 3 inhibited Gram-positive bacteria Bacillus subtilis, Lactobacillus cereus and Staphylococcus aureus and exhibited antifungal activity against the pathogenic fungus F. solani. The mode-of-action of these antimicrobial sesquiterpenes as bacterial type II DNA topoisomerase and/or DNA gyrase B inhibitors were examined via in silico studies. Such molecular-docking studies were also employed to examine antifungal activity against an N-myristoyl transferase (NMT) target. Compound 3 had the greatest gyrase B binding affinity in the ATP-binding pocket and was found to possess an inhibitory action against non-invasive micro-test technology (NMT).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Identified metabolites (1–3).
Fig. 2
Fig. 2. Observed 1H–1H COSY and HMBC correlations (shown in blue and red, respectively) for 1–2.
Fig. 3
Fig. 3. Observed NOESY correlations for 1–2.
Fig. 4
Fig. 4. Newman projections [A] H-11 displays data for the coupling constants (JH7–11 = 11.7 Hz) and (JH11–13 = 7.0 Hz) in a pseudo-axial orientation. [B] (JH7–11 = 7.7 Hz) and (JH11–13 = 7.0 Hz) are values of the coupling constants which might be seen in the pseudo-equatorial configuration of H-11. [C] Confirmed that compound 2 virtually completely dismisses the coupling between H-7 and H-11.
Fig. 5
Fig. 5. 2D and 3D representations of the predicted binding modes inside the active site of the bacterial 4GEE for compounds 1–3.
Fig. 6
Fig. 6. 2D and 3D representations of the predicted binding modes inside the fungal active site of 1IYK for compounds 1–3.
See this image and copyright information in PMC

References

    1. Newman D. J. Cragg G. M. J. Nat. Prod. 2016;79:629–661. - PubMed
    1. Pan S.-Y. Litscher G. Gao S.-H. Zhou S.-F. Yu Z.-L. Chen H.-Q. Zhang S.-F. Tang M.-K. Sun J.-N. Ko K.-M. Evid.-Based Complementary Altern. Med. 2014;2014:1–20.
    1. Anand U. Jacobo-Herrera N. Altemimi A. Lakhssassi N. Metabolites. 2019;9:258. - PMC - PubMed
    1. Anand U. Nandy S. Mundhra A. Das N. Pandey D. K. Dey A. Drug Resistance Updates. 2020;51:100695. - PubMed
    1. Gorlenko C. L. Kiselev H. Y. Budanova E. V. Zamyatnin Jr A. A. Ikryannikova L. N. Antibiotics. 2020;9:170. - PMC - PubMed