Synthesis, Crystal Structure, Antibacterial and In Vitro Anticancer Activity of Novel Macroacyclic Schiff Bases and Their Cu (II) Complexes Derived from <i>S</i>-Methyl and <i>S</i>-Benzyl Dithiocarbazate
Mohammed Khaled Bin Break,
Tan Yew Fung,
May Zie Koh,
Wan Yong Ho,
Mohamed Ibrahim Mohamed Tahir,
Omar Ashraf Elfar,
Rahamat Unissa Syed,
Weam M. A. Khojali,
Turki Mubarak Alluhaibi,
Bader Huwaimel,
Christophe Wiart,
Teng-Jin Khoo
Affiliations
Mohammed Khaled Bin Break
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 55473, Saudi Arabia
Tan Yew Fung
School of Pharmacy, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih 43500, Selangor, Malaysia
May Zie Koh
Division of Biomedical Sciences, School of Pharmacy, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih 43500, Selangor, Malaysia
Wan Yong Ho
Division of Biomedical Sciences, School of Pharmacy, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih 43500, Selangor, Malaysia
Mohamed Ibrahim Mohamed Tahir
Department of Chemistry, Faculty of Science, University Putra Malaysia, Serdang 43400, Selangor, Malaysia
Omar Ashraf Elfar
School of Pharmacy, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih 43500, Selangor, Malaysia
Rahamat Unissa Syed
Medical and Diagnostic Research Centre, University of Hail, Hail 55473, Saudi Arabia
Weam M. A. Khojali
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 55473, Saudi Arabia
Turki Mubarak Alluhaibi
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 55473, Saudi Arabia
Bader Huwaimel
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail 55473, Saudi Arabia
Christophe Wiart
Institute for Tropical Biology & Conservation, University Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
Teng-Jin Khoo
School of Pharmacy, Faculty of Science and Engineering, University of Nottingham Malaysia, Semenyih 43500, Selangor, Malaysia
A series of novel macroacyclic Schiff base ligands and their Cu (II) complexes were synthesised via reacting dicarbonyls of varying chain lengths with S-methyl dithiocarbazate (SMDTC) and S-benzyl dithiocarbazate (SBDTC) followed by coordination with Cu (II) ions. X-ray crystal structures were obtained for compound 4, an SBDTC-diacetyl analogue, and Cu7, an SMDTC-hexanedione Cu (II) complex. Anticancer evaluation of the compounds showed that Cu1, an SMDTC-glyoxal complex, demonstrated the highest cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer cells with IC50 values of 1.7 µM and 1.4 µM, respectively. There was no clear pattern observed between the effect of chain length and cytotoxic activity; however, SMDTC-derived analogues were more active than SBDTC-derived analogues against MDA-MB-231 cells. The antibacterial assay showed that K. rhizophila was the most susceptible bacteria to the compounds, followed by S. aureus. Compound 4 and the SMDTC-derived analogues 3, 5, Cu7 and Cu9 possessed the highest antibacterial activity. These active analogues were further assessed, whereby 3 possessed the highest antibacterial activity with an MIC of K. rhizophila and S. aureus. Further antibacterial studies showed that at least compounds 4 and 5 were bactericidal. Thus, Cu1 and 3 were the most promising anticancer and antibacterial agents, respectively.
