Synthesis, pharmacological profile and 2D-QSAR studies of curcumin-amino acid conjugates as potential drug candidates

Siva S Panda; Adel S Girgis; Sean J Thomas; Jason E Capito; Riham F George; Asmaa Salman; May A El-Manawaty; Ahmed Samir

doi:10.1016/j.ejmech.2020.112293

Synthesis, pharmacological profile and 2D-QSAR studies of curcumin-amino acid conjugates as potential drug candidates

Eur J Med Chem. 2020 Jun 15:196:112293. doi: 10.1016/j.ejmech.2020.112293. Epub 2020 Apr 6.

Authors

Siva S Panda¹, Adel S Girgis², Sean J Thomas³, Jason E Capito³, Riham F George⁴, Asmaa Salman⁵, May A El-Manawaty⁶, Ahmed Samir⁷

Affiliations

¹ Department of Chemistry and Physics, Augusta University, Augusta, GA, 30912, USA. Electronic address: sspanda12@gmail.com.
² Department of Pesticide Chemistry, National Research Centre, Dokki, Giza, 12622, Egypt.
³ Department of Chemistry and Physics, Augusta University, Augusta, GA, 30912, USA.
⁴ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
⁵ Medical and Pharmaceutical Chemistry Department, National Research Centre, Dokki, Giza, 12622, Egypt.
⁶ Drug Bioassay-Cell Culture Laboratory, Pharmacognosy Department, National Research Centre, Dokki, Giza, 12622, Egypt.
⁷ Microbiology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.

PMID: 32311607
DOI: 10.1016/j.ejmech.2020.112293

Abstract

A series of curcumin bis-conjugates 3a-q, 5a-k and 6a-k were synthesized in good yields utilizing an optimized reaction condition. We explored the effect of different amino acids and protecting groups on biological activities of curcumin. The conjugates were screened for anti-inflammatory, analgesic and antimicrobial properties. Some of the conjugates showed promising biological observations with a potency comparable with the standard references. The variations in biological properties concerning different amino acids and protecting groups are interesting observations. Effects of the synthesized conjugates on splenocytes and the production of nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages are correlated with the observed anti-inflammatory properties. We have also established the safety profile of the most active conjugates. Robust 2D-QSAR studies supported and validated biological data.

Keywords: 2D-QSAR; Amino acid; Analgesic; Anti-inflammatory; Antimicrobial; Curcumin; Prodrug.

MeSH terms

Amino Acids / chemistry
Amino Acids / pharmacology*
Analgesics / chemical synthesis
Analgesics / chemistry
Analgesics / pharmacology*
Animals
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antifungal Agents / chemical synthesis
Antifungal Agents / chemistry
Antifungal Agents / pharmacology*
Candida albicans / drug effects
Carrageenan
Cell Proliferation / drug effects
Curcumin / chemistry
Curcumin / pharmacology*
Dose-Response Relationship, Drug
Edema / chemically induced
Edema / drug therapy
Mice
Microbial Sensitivity Tests
Molecular Structure
Pain / drug therapy
Pseudomonas aeruginosa / drug effects
Quantitative Structure-Activity Relationship
Rats
Salmonella typhi / drug effects
Spleen / drug effects
Staphylococcus aureus / drug effects
Streptococcus pyogenes / drug effects
Ulcer / drug therapy

Substances

Amino Acids
Analgesics
Anti-Bacterial Agents
Anti-Inflammatory Agents, Non-Steroidal
Antifungal Agents
Carrageenan
Curcumin