Organometallic Compounds and Metal Complexes in Current and Future Treatments of Inflammatory Bowel Disease and Colorectal Cancer—a Critical Review

Szczepaniak, Adrian; Fichna, Jakub

doi:10.3390/biom9090398

Cited by 18 publications

(10 citation statements)

References 101 publications

(134 reference statements)

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“…Since the discovery of platinum anticancer properties and the use of cisplatin, a platinum-based alkylating agent, and its derivatives in chemotherapy (37)(38)(39), other metal-based drugs have been designed and developed for their cytotoxic effects on tumour cells (40)(41)(42). Transition metals from the d-block of the periodic table (groups 3 to 12) (43)(44)(45)(46) are particularly suitable for this purpose as they adopt a wide variety of coordination geometries (47). Among them, copper modifies the backbone of the complexed ligand and grants better DNA affinity (48)(49)(50).…”

Section: Introductionmentioning

confidence: 99%

A Novel Copper(II) Indenoisoquinoline Complex Inhibits Topoisomerase I, Induces G2 Phase Arrest, and Autophagy in Three Adenocarcinomas

Molinaro

Wambang

Bousquet³

et al. 2022

Front. Oncol.

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Topoisomerases, targets of inhibitors used in chemotherapy, induce DNA breaks accumulation leading to cancer cell death. A newly synthesized copper(II) indenoisoquinoline complex WN197 exhibits a cytotoxic effect below 0.5 µM, on MDA-MB-231, HeLa, and HT-29 cells. At low doses, WN197 inhibits topoisomerase I. At higher doses, it inhibits topoisomerase IIα and IIβ, and displays DNA intercalation properties. DNA damage is detected by the presence of γH2AX. The activation of the DNA Damage Response (DDR) occurs through the phosphorylation of ATM/ATR, Chk1/2 kinases, and the increase of p21, a p53 target. WN197 induces a G2 phase arrest characterized by the unphosphorylated form of histone H3, the accumulation of phosphorylated Cdk1, and an association of Cdc25C with 14.3.3. Cancer cells die by autophagy with Beclin-1 accumulation, LC3-II formation, p62 degradation, and RAPTOR phosphorylation in the mTOR complex. Finally, WN197 by inhibiting topoisomerase I at low concentration with high efficiency is a promising agent for the development of future DNA damaging chemotherapies.

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Section: Introductionmentioning

confidence: 99%

A Novel Copper(II) Indenoisoquinoline Complex Inhibits Topoisomerase I, Induces G2 Phase Arrest, and Autophagy in Three Adenocarcinomas

Molinaro

Wambang

Bousquet³

et al. 2022

Front. Oncol.

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“…Silver nanoparticles (AgNPs) are one of the metal nanoparticle types viewed as potential topical anti-inflammatory agent for treatment of inflammatory bowel diseases (IBDs) such as Crohn's disease, ulcerative colitis, and colonic cancer [1][2][3]. The intestinal inflammation disorder mediated by the immune system is a typical feature of IBD.…”

Section: Introduction mentioning

confidence: 99%

“…Inflammation is a natural body's response to tissue damage. However, it can cause improper tissue repair and contribute to the development of cancer through genotoxic mechanism in the longterm [1]. In-vitro studies reported that AgNPs show drugs can take place in colon.…”

Section: Introduction mentioning

confidence: 99%

Potentials of Alginates as Capping Agent for Oral Colon Delivery of Radiosynthesized Silver Nanoparticles: A Review

2022

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Radiosynthesized silver nanoparticles (AgNPs) offer benefits for treatment of chronic colon inflammation due to their anti-inflammatory activity. Targeted delivery of AgNPs to the colon allows topical treatment at high concentration but at reduced systemic side effects. Meanwhile, related to drug administration, oral route is a common method. However, the physiology of the gastrointestinal (GI) tract limits the AgNPs ability to achieve their therapeutic level. This is specifically related to the acidic environment of the stomach and mucus layer of the GI tract. Concurently, alginates are one of the most extensively explored biomaterial classes for drug delivery system due to its biocompatibility, gel-forming ability at mild condition, anionic nature, sensitivity, and mucoadhesiveness. In this review we provide an overview of appropriate features of alginates as capping agent for oral delivery of radiosynthesized AgNPs to the colon. As capping agents, alginates play multiple roles specific to its processing stages, i.e., radiosynthesis, stabilization of nanoparticle system, and oral colon delivery devices of AgNPs. Additionally, we describe outstanding features of alginates as capping agents for drug delivery device as well as the positive contributions of radiation processing on improving the functional effects of alginate.

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“…[2][3][4][5][6][7][8] Transition metal complexes have emerged as a viable alternative to organic compounds with distinct biological properties and have been wildly utilized for the treatment of cancer. [9][10] Recently, transition metal complexes have been developed as chemical reagents capable of altering Aβ aggregation. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Among many of these transition metal complexes, cyclometalated Ir(III) complexes would be one of the most promising candidates as their photophysical and photochemical properties are unique and desirable.…”

Section: Introductionmentioning

confidence: 99%

Blood-Brain Barrier Permeable 2-Phenylbenzothiazolyl Iridi-um Complexes as Inhibitors and Probes of Aβ Aggregation

Huang¹,

Na²,

Sun³

et al. 2021

Preprint

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The aggregation of amyloid β (Aβ) peptides is a significant hallmark of Alzheimer’s Disease (AD) and the inhibition and detection of Aβ aggregates are important for the treatment and diagnosis of AD. Herein, a series of benzothiazole-based luminescent Ir(III) complexes HN-1 to HN-8 were reported, which exhibit appreciable Aβ aggregation inhibition ability in vitro and in living cells. In addition, they are capable of inducing a fluorescence turn-on effect when binding to Aβ fibrils and oligomers. Most importantly, compared to previously reported cationic metal complexes, the neutral Ir complexes reported here show optimal Log D values, which suggest these compounds should have enhanced blood brain barrier (BBB) permeability. Most importantly, in vivo studies show that the neutral Ir complexes HN-2, HN-3, and HN-8 successfully penetrate the BBB and stain amyloid plaques in AD mice brains after a 10-day treatment via i.p. injection, which is unprecedented for Ir(III) complexes, and thus can be used as lead compounds for AD therapeutics development.

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Organometallic Compounds and Metal Complexes in Current and Future Treatments of Inflammatory Bowel Disease and Colorectal Cancer—a Critical Review

Cited by 18 publications

References 101 publications

A Novel Copper(II) Indenoisoquinoline Complex Inhibits Topoisomerase I, Induces G2 Phase Arrest, and Autophagy in Three Adenocarcinomas

A Novel Copper(II) Indenoisoquinoline Complex Inhibits Topoisomerase I, Induces G2 Phase Arrest, and Autophagy in Three Adenocarcinomas

Potentials of Alginates as Capping Agent for Oral Colon Delivery of Radiosynthesized Silver Nanoparticles: A Review

Blood-Brain Barrier Permeable 2-Phenylbenzothiazolyl Iridi-um Complexes as Inhibitors and Probes of Aβ Aggregation

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