Synthesis, Characterization, and Biological Evaluation of Meldrum’s Acid Derivatives: Dual Activity and Molecular Docking Study-Reference-Cited by-同舟云学术

Synthesis, Characterization, and Biological Evaluation of Meldrum’s Acid Derivatives: Dual Activity and Molecular Docking Study

Published:2023-02-13 Issue:2 Volume:16 Page:281
ISSN:1424-8247
Container-title:Pharmaceuticals
language:en
Short-container-title:Pharmaceuticals

Author:

Bukhari Syed Nasir Abbas¹^ORCID,Abdelgawad Mohamed Abdelwahab¹^ORCID,Ahmed Naveed²^ORCID,Amjad Muhammad Wahab³^ORCID,Hussain Muhammad Ajaz⁴^ORCID,Elsherif Mervat A.⁵,Ejaz Hasan⁶^ORCID,Alotaibi Nasser H.⁷,Filipović Ignjat⁸^ORCID,Janković Nenad⁹^ORCID

Affiliation:

1. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia

2. Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia

3. Center for Ultrasound Molecular Imaging and Therapeutics, Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA

4. Centre for Organic Chemistry, School of Chemistry, University of the Punjab, Lahore 54590, Pakistan

5. Chemistry Department, College of Science, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia

6. Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia

7. Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Sakaka 72388, Al Jouf, Saudi Arabia

8. University of Kragujevac, Faculty of Science, Radoja Domanovića 12, 34000 Kragujevac, Serbia

9. University of Kragujevac, Department of Science, Institute for Information Technologies Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia

Abstract

In the presented study, eight novel Meldrum’s acid derivatives containing various vanillic groups were synthesized. Vanillidene Meldrum’s acid compounds were tested against different cancer cell lines and microbes. Out of nine, three showed very good biological activity against E. coli, and HeLa and A549 cell lines. It is shown that the O-alkyl substituted derivatives possessed better antimicrobial and anticancer activities in comparison with the O-acyl ones. The decyl substituted molecule (3i) has the highest activity against E. coli (MIC = 12.4 μM) and cancer cell lines (HeLa, A549, and LS174 = 15.7, 21.8, and 30.5 μM, respectively). The selectivity index of 3i is 4.8 (HeLa). The molecular docking study indicates that compound 3i showed good binding affinity to DNA, E. coli Gyrase B, and topoisomerase II beta. The covalent docking showed that 3i was a Michael acceptor for the nucleophiles Lys and Ser. The best Eb was noted for the topoisomerase II beta-LYS482-3i cluster.

Funder

Deanship of Scientific Research

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

Link

https://www.mdpi.com/1424-8247/16/2/281/pdf

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