Biological effects and activity optimization of small-molecule, drug-like synthetic anion transporters

Yu, Xi-Hui; Hong, Xiao-Qiao; Mao, Qin-Chao; Chen, Wenhua

doi:10.1016/j.ejmech.2019.111782

Cited by 18 publications

(9 citation statements)

References 102 publications

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“…In addition to cations, anion homeostasis in cells also has a great impact on cell life activities. The balance of normal anion concentration in cells provides a basis for maintaining cell morphology and function [ 38 ]. Compared with normal cells, cancer cells are more sensitive to anion homeostasis [ 38 ].…”

Section: Ion Interference Therapymentioning

confidence: 99%

“…The balance of normal anion concentration in cells provides a basis for maintaining cell morphology and function [ 38 ]. Compared with normal cells, cancer cells are more sensitive to anion homeostasis [ 38 ]. Therefore, interfering with anion homeostasis in cancer cells is also an effective means to achieve cancer treatment.…”

Section: Ion Interference Therapymentioning

confidence: 99%

“…Chloridion, as the most common anion in cells, has been widely studied. Synthetic anion transporters, a type of small molecular organic compound with transmembrane anion transport activity, can interfere with the homeostasis of cell anions, especially chloride ions, and trigger cell death [ 38 ]. Adil S. Aslam et al proved that disturbed chloride ion concentration induced by an ion transporter in a cellular level affects endoplasmic reticulum (ER) stress by increasing Ca 2+ concentration, and leads to apoptosis [ 39 ].…”

Section: Ion Interference Therapymentioning

confidence: 99%

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Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles

et al. 2022

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As an essential substance for cell life activities, ions play an important role in controlling cell osmotic pressure balance, intracellular acid–base balance, signal transmission, biocatalysis and so on. The imbalance of ion homeostasis in cells will seriously affect the activities of cells, cause irreversible damage to cells or induce cell death. Therefore, artificially interfering with the ion homeostasis in tumor cells has become a new means to inhibit the proliferation of tumor cells. This treatment is called ion interference therapy (IIT). Although some molecular carriers of ions have been developed for intracellular ion delivery, inorganic nanoparticles are widely used in ion interference therapy because of their higher ion delivery ability and higher biocompatibility compared with molecular carriers. This article reviewed the recent development of IIT based on inorganic nanoparticles and summarized the advantages and disadvantages of this treatment and the challenges of future development, hoping to provide a reference for future research.

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Section: Ion Interference Therapymentioning

confidence: 99%

Section: Ion Interference Therapymentioning

confidence: 99%

Section: Ion Interference Therapymentioning

confidence: 99%

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Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles

et al. 2022

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“…This costly and time consuming process is being replaced by Virtual Screening (VS). VS uses computational models including IFTs ( Yu et al, 2019 ) to predict how a compound will interact with the target thus greatly reducing both costs and time. Fragment Based Drug Discovery (FBDD) is a low cost and potentially more rapid alternative approach to assist drug discovery that utilises small molecules to enhance drug uptake.…”

Section: Fragment Based Drug Discoverymentioning

confidence: 99%

Cell Surface Transporters and Novel Drug Developments

Carmichael

Day

2022

Front. Pharmacol.

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Despite the numerous scientific and technological advances made within the last decade the attrition rates for new drug discovery remain as high as 95% for anticancer drugs. Recent drug development has been in part guided by Lipinski’s Rule of 5 (Ro5) even though many approved drugs do not comply to these rules. With Covid-19 vaccine development strategy dramatically accelerating drug development perhaps it is timely to question the generic drug development process itself to find a more efficient, cost effective, and successful approach. It is widely believed that drugs permeate cells via two methods: phospholipid bilayer diffusion and carrier mediated transporters. However, emerging evidence suggests that carrier mediated transport may be the primary mechanism of drug uptake and not diffusion as long believed. Computational biology increasingly assists drug design to achieve desirable absorption, distribution, metabolism, elimination and toxicity (ADMET) properties. Perfecting drug entry into target cells as a prerequisite to intracellular drug action is a logical and compelling route and is expected to reduce drug attrition rates, particularly gaining favour amongst chronic lifelong therapeutics. Novel drug development is rapidly expanding from the utilisation of beyond the rule of five (bRo5) to pulsatile drug delivery systems and fragment based drug design. Utilising transporters as drug targets and advocating bRo5 molecules may be the solution to increasing drug specificity, reducing dosage and toxicity and thus revolutionising drug development. This review explores the development of cell surface transporter exploitation in drug development and the relationship with improved therapeutic index.

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“…Anion binding and transport play an important role in many biological processes, such as signal transduction, metabolism, osmosis, and pH regulation. , Malfunction of the proteins that are involved in anion transport can lead to severe illnesses, e.g., Dent disease, Bartter’s syndrome, and cystic fibrosis . This has inspired intensive studies on synthetic anion receptors that are capable of facilitating the transport of anions across the phospholipid bilayer. ,− Small molecules serving as anion transporters exhibit excellent potential in treating diseases caused by defective anion transport. ,, Especially, photoswitchable compounds, such as spiropyran, azobenzene (AB), and stiff-stilbene, which have reportedly highly tunable anion binding affinity upon configuration change caused by photoisomerization, as observed, have aroused increasing interest in the area of biological membrane transporters. − …”

Section: Introductionmentioning

confidence: 99%

Azopyrazole-Based Photoswitchable Anion Receptor for Dihydrogen Phosphate Transport

Yang

et al. 2020

J. Phys. Chem. A

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Small-molecule anion carriers are potential reagents used in the treatment of diseases caused by dysregulated anion transport. Photoswitchable anion receptors, which can be reversibly switched between isomers by light and thereby cause reversible changes in anion binding affinity, have been receiving enormous interest. Here, based on the well-known photoswitch 1-N-methyl-3-phenylazopyrazole (3pzH), we designed a novel tetramethylamide-3pzH (3pzH_TA) photoswitchable receptor that achieves highly efficient and durable anion transportation. It enables high photoisomerization ratios of E → Z (>98%) and Z → E (97%) with a thermal half-life two times longer than that of 3pzH. We further demonstrated the high sensitivity of 3pzH_TA toward H 2 PO 4 − anion and revealed the key role of hydrogen bonds between H 2 PO 4 − and Z isomer in the strength of anion binding. Our findings open up a new strategy for the rational design and understanding of new types of photoswitchable anion receptors.

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Biological effects and activity optimization of small-molecule, drug-like synthetic anion transporters

Cited by 18 publications

References 102 publications

Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles

Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles

Cell Surface Transporters and Novel Drug Developments

Azopyrazole-Based Photoswitchable Anion Receptor for Dihydrogen Phosphate Transport

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