Development of synthetic chloride transporters using high-throughput screening and machine learning.

The development of synthetic compounds capable of transporting chloride anions across biological membranes has become an intensive research field in the last two decades. Progress is driven by the desire to develop treatments for chloride transport related diseases (, cystic fibrosis), cancer or bacterial infections. In this manuscript, we use high-throughput screening and machine learning to identify novel scaffolds, and to find the molecular features needed to achieve potent chloride transport that can be generalized across diverse chemotypes.

Medical and Nonmedical Applications of Synthetic Transmembrane Anion Transporters.

The transport of anionic species across phospholipid bilayers is an important biological function that plays a vital role in cellular and organismal homeostasis. The function is normally performed by transmembrane transport proteins, but several diseases have been linked to malfunctioning or malregulation of these proteins (so-called "channelopathies"). As a consequence, supramolecular chemists have tried to develop synthetic molecules that can transport anions across biological membranes.

Increasing membrane permeability of carboxylic acid-containing drugs using synthetic transmembrane anion transporters.

In this manuscript, we show that small-molecule-based anion transporters can significantly increase the permeability of carboxylic acid containing drugs across lipid bilayers of model vesicles. Due to the drug-like characteristics of the transporters, this finding could not only have implications for drug delivery, but also hints towards potential drug-drug and drug-food interactions.

Antiviral Peptides as Promising Therapeutics against SARS-CoV-2.

Over 50 peptides, which were known to inhibit SARS-CoV-1, were computationally screened against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Based on the binding affinity and interaction, 15 peptides were selected, which showed higher affinity compared to the α-helix of the human ACE2 receptor. Molecular dynamics simulation demonstrated that two peptides, S2P25 and S2P26, were the most promising candidates, which could potentially block the entry of SARS-CoV-2.

design and evaluation of novel 5-fluorouracil analogues as potential anticancer agents.

5-fluorouracil (5-FU) has been shown to have suffered from resistance which demands a solution entailing the development of 5-FU analogues. Our study aims to design a number of analogues of 5-FU and evaluate their effectiveness against thymidylate synthase (TS) compared to parent 5-FU with an effort to obtain better hit(s). All the molecules were optimized by molecular mechanics method utilizing MM2 forcefield parameters.

DPYD*2A and MTHFR C677T predict toxicity and efficacy, respectively, in patients on chemotherapy with 5-fluorouracil for colorectal cancer.

Background: Significant inter-individual variation in the sensitivity to 5-fluorouracil (5-FU) represents a major therapeutic hindrance either by impairing drug response or inducing adverse drug reactions (ADRs). This study aimed at exploring the cause behind this inter-individual alterations in consequences of 5-fluorouracil-based chemotherapy by investigating the effects of DPYD*2A and MTHFR C677T polymorphisms on toxicity and response of 5-FU in Bangladeshi colorectal cancer patients.

Methods: Colorectal cancer patients (n = 161) receiving 5-FU-based chemotherapy were prospectively enrolled.