Development of Natural Product-Conjugated Metal Complexes as Cancer Therapies

Ma, Dik‐Lung; Wu, Cheng‐Shyong; Cheng, Shasha; Lee, Fu-Wa; Han, Quan‐Bin; Leung, Chung‐Hang

doi:10.3390/ijms20020341

Cited by 38 publications

(20 citation statements)

References 80 publications

(86 reference statements)

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“…CoMeDs combines two different agents, such as silver(I) with penicillin to create new agents with new properties from the superimposition of those initially possessed by the constituents [6][7][8][9][10][11][12]. Although the term "conjugate" is more properly used for polymer-drugs or dendrimer-drug conjugates where nanoparticles are formed, recently, the term CoMeD has also been used to emphasize the synergistic effect of the coordination of a metal with drugs [13,14]. Furthermore, the solvent type affects the structure of the metal-drug complexes, leading to the formation of polymeric structures by the metal-drug-solvent conjugation.…”

Section: Introductionmentioning

confidence: 99%

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

et al. 2020

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Conjugation of penicillin G (PenH) with silver(I) ions forms a new CoMeD (conjugate of metal with a drug) with formula [Ag(pen)(CH3OH)]2 (PenAg). PenAg was characterized by a plethora of physical and spectroscopic techniques, which include in the solid state m.p.; elemental analysis; X-ray fluorescence (XRF) spectroscopy; scanning electron microscopy (SEM); energy-dispersive X-ray spectroscopy (EDX); FT-IR; and in solution: attenuated total reflection spectroscopy (FT-IR-ATR), UV–Vis, 1H NMR, and atomic absorption (AA). The structure of PenAg was determined by NMR spectroscopy. Silver(I) ions coordinate to the carboxylic group of PenH, while secondary intra-molecular interactions are developed through (i) the nitrogen atom of the amide group in MeOD-d4 or (ii) the sulfur atom in the thietane ring in deuterated dimethyl sulfoxide DMSO-d6. The antibacterial activities of PenAg and the sodium salt of penicillin (PenNa) (the formulation which is clinically used) against Gram positive (Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus)) and Gram negative (Pseudomonas aeruginosa (P. aeuroginosa PAO1)) bacteria were evaluated by the means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and inhibition zone (IZ). PenAg inhibits the growth of the Gram negative bacterial strain P. aeuroginosa with a MIC value of 23.00 ± 2.29 μM, in contrast to PenNa, which shows no such activity (>2 mM). The corresponding antimicrobial activities of PenAg against the Gram positive bacteria S. epidermidis and S. aureus are even better than those of PenNa. Moreover, PenAg exhibits no in vivo toxicity against Artemia salina at concentration up to 300 μΜ. The wide therapeutic window and the low toxicity, make PenAg a possible candidate for the development of a new antibiotic.

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Section: Introductionmentioning

confidence: 99%

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

et al. 2020

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“…In recent years, the development of agents with enhanced anticancer properties via the coordination of biologically active molecules to metals, more specifically ruthenium, has attracted increasing attention [36][37][38]. Because ruthenium complexes are widely studied for their ability to induce cancer cell death, the introduction of biologically active ligands in their structure can be a promising approach for the development of drug candidates with a broader range of anticancer activities compared to ruthenium complexes or ligands alone [39,40].…”

Section: Introductionmentioning

confidence: 99%

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy

Golbaghi

Castonguay

2020

Molecules

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Since the discovery of the anticancer potential of ruthenium-based complexes, several species were reported as promising candidates for the treatment of breast cancer, which accounts for the greatest number of new cases in women every year worldwide. Among these ruthenium complexes, species containing bioactive ligand(s) have attracted increasing attention due to their potential multitargeting properties, leading to anticancer drug candidates with a broader range of cellular targets/modes of action. This review of the literature aims at providing an overview of the rationally designed ruthenium-based complexes that have been reported to date for which ligands were carefully selected for the treatment of hormone receptor positive breast cancers (estrogen receptor (ER+) or progesterone receptor (PR+)). In addition, this brief survey highlights some of the most successful examples of ruthenium complexes reported for the treatment of triple negative breast cancer (TNBC), a highly aggressive type of cancer, regardless of if their ligands are known to have the ability to achieve a specific biological function.

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“…The precursor cobalt(III) complexes [Co(B) 2 Cl 2 ]Cl (B = phen, dpq, and dppz) were prepared by oxidizing the corresponding cobalt(II) complexes using dry chlorine gas . Dry chlorine gas was prepared in situ by reacting KMnO 4 with concentrated hydrochloric acid and passing the resulting gas through concentrated sulfuric acid …”

Section: Methodsmentioning

confidence: 99%

“…Natural products have gained popularity as emerging sources for developing anticancer drugs, and the role of natural products in designing PDT drugs has recently been highlighted. , Esculetin (6,7-dihydroxycoumarin) is a naturally occurring coumarin derivative found in plants and is known to possess significant anticancer activity against various cancers . Studies have shown that esculetin can act as a photosensitizer for DNA damage .…”

Section: Introductionmentioning

confidence: 99%

Mixed-Ligand Cobalt(III) Complexes of a Naturally Occurring Coumarin and Phenanthroline Bases as Mitochondria-Targeted Dual-Purpose Photochemotherapeutics

Sarkar¹,

Kumar

Sahoo

et al. 2021

Inorg. Chem.

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The bioessential nature of cobalt and the rich photochemistry of its coordination complexes can be exploited to develop potential next-generation photochemotherapeutics. A series of six novel mixed-ligand cobalt(III) complexes of the formulation [Co(B)2(L)]ClO4 (1–6), where B is an N,N-donor phenanthroline base, namely, 1,10-phenanthroline (phen in 1 and 4), dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq in 2 and 5), and dipyrido[3,2-a:2′,3′-c]phenazine (dppz in 3 and 6), and L is an O,O-donor dianionic ligand derived from catechol (1,2-dihydroxybenzene, cat2–, in 1–3) or esculetin (6,7-dihydoxycoumarin, esc2–, in 4–6), have been prepared and characterized, and their light-triggered cytotoxicity has been studied in cancer cells. The single-crystal X-ray diffraction structures of complexes 1 (as PF6 – salt, 1a) and 2 show distorted octahedral geometries around the cobalt(III) center formed by the set of N4O2 donor atoms. The low-spin and 1:1 electrolytic complexes 1–6 display a d–d transition around 700 nm. Complexes 4–6 with a coordinated esc2– ligand additionally display a π → π* intraligand transition centered at 403 nm. Complexes 4–6 possessing a naturally occurring and photoactive esc2– ligand show high visible-light-triggered cytotoxicity against HeLa and MCF-7 cancer cells, yielding remarkably low micromolar IC50 values while being much less toxic under dark conditions. Control complexes 1–3 possessing the photoinactive cat2– ligand show significantly less cytotoxicity either in the presence of light or in the dark. The complex-induced cell death is apoptotic in nature caused by the formation of reactive oxygen species via a type 1 photoredox pathway. Fluorescence microscopy of HeLa cells treated with complex 6 reveals mitochondrial localization of the complex. A significant decrease in the dark toxicity of free esculetin and dppz base is observed upon coordination to cobalt(III). Complexes bind to calf-thymus DNA with significant affinity, but 6 binds with the greatest affinity. Complex 6 efficiently photocleaves supercoiled DNA to its nicked circular form when irradiated with visible light via a photoredox type 1 pathway involving hydroxyl radicals (HO•). Thus, complex 6 showing remarkable visible-light-triggered cytotoxicity but negligible toxicity in the dark is a good candidate for cancer photochemotherapy applications.

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Development of Natural Product-Conjugated Metal Complexes as Cancer Therapies

Cited by 38 publications

References 80 publications

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

Conjugation of Penicillin-G with Silver(I) Ions Expands Its Antimicrobial Activity against Gram Negative Bacteria

Rationally Designed Ruthenium Complexes for Breast Cancer Therapy

Mixed-Ligand Cobalt(III) Complexes of a Naturally Occurring Coumarin and Phenanthroline Bases as Mitochondria-Targeted Dual-Purpose Photochemotherapeutics

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