Surveillance of veterinary drug residues in food commonly consumed in Singapore and assessment of dietary exposure.

Non-judicious and indiscriminate use of veterinary drugs in animal husbandry may result in accumulation of residues in animal tissues, and consequently in food for human consumption. The abuse of veterinary drugs presents a potential risk to consumer health, especially if the residue level is higher than the health-based guidance value (HBGV) such as the acceptable daily intake (ADI). Contamination of drug residues in food also promotes the emergence of antimicrobial resistance (AMR) which poses a serious threat to public health globally. There has been limited information on the occurrence and dietary exposure to veterinary drug residues in Singapore to date. In this study, the occurrence of four classes of veterinary drugs, namely beta-agonists, coccidiostats, fluoroquinolones and macrolides, were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in food widely consumed by Singapore residents. The magnitude of dietary exposure was assessed based on the consumption profile of Singapore population. Out of 216 food samples, 9.72 % were detected positive with veterinary drug residues, where majority of the positive samples were poultry and its derived products, followed by eggs and egg products. 7 veterinary drugs, specifically ciprofloxacin, enrofloxacin, clopidol, diclazuril, lasalocid, nicarbazin and tilmicosin, were detected in the samples, with clopidol and enrofloxacin being the most frequently detected drugs. Dietary exposure was evaluated using the estimated daily intake (EDI) of the detected drugs and benchmarked against the corresponding acceptable daily intake (ADI). All the %ADI values were far less than 100 in both the average and high consumer scenarios, indicating that the health risk associated with dietary exposure to these drugs in Singapore is low.

Discovery of novel dual VEGFR2 and Src inhibitors using a multistep virtual screening approach.

AIM: Simultaneous inhibition of VEGFR2 and Src may enhance the efficacy of VEGFR2-targeted cancer therapeutics. Hence, development of dual inhibitors on VEGFR2 and Src can be a useful strategy for such treatments. MATERIALS & METHODS: A multistep virtual screening protocol, comprising ligand-based support vector machines method, drug-likeness rules filter and structure-based molecular docking, was developed and employed to identify dual inhibitors of VEGFR2 and Src from a large commercial chemical library. Kinase inhibitory assays and cell viability assays were then used for experimental validation. RESULTS: A set of compounds belonging to six different molecular scaffolds was identified and sent for biological evaluation. Compound 3c belonging to the 2-amino-3-cyanopyridine scaffold exhibited good antiproliferative effect and dual-target activities against VEGFR2 and Src. CONCLUSION: This study demonstrated the ability of the multistep virtual screening approach to identify novel multitarget agents.