Anticancer drug resistance is one of the biggest hurdles in the treatment of breast cancer. Drug repurposing is a viable option fordeveloping novel medical treatment strategies since this method is more cost-efficient and rapid. Antihypertensive medicines have recently been found to have pharmacological features that could be used to treat cancer, making them effective candidates for therapeutic repurposing. The goal of our research is to find a potent antihypertensive drug that can be repurposed as adjuvant therapy for breast cancer. In this study, virtual screening was performed using a set of Food and Drug Administration (FDA)-approved antihypertensive drugs as ligands with selected receptor proteins (EGFR, KRAS, P53, AGTR1, AGTR2, and ACE) assuming these proteins are regarded to have a significant role in hypertension as well as breast cancer. Further, our in-silico results were further confirmed by an in-vitro experiment (cytotoxicity assay). All the compounds (enalapril, atenolol, acebutolol, propranolol, amlodipine, verapamil, doxazosin, prazosin, hydralazine, irbesartan, telmisartan, candesartan, and aliskiren) showed remarkable affinity towards the target receptor proteins. However, maximum affinity was displayed by telmisartan. Cell-based cytotoxicity study of telmisartan in MCF7 (breast cancer cell line) confirmed the anticancer effect of telmisartan. IC50 of the drug was calculated to be 7.75 µM and at this concentration, remarkable morphological alterations were observed in the MCF7 cells confirming its cytotoxicity in breast cancer cells. Based on both in-silico and in-vitro studies, we can conclude that telmisartan appears to be a promising drug repurposing candidate for the therapeutic treatment of breast cancer.

Introduction: Use of natural products for management of diseases has increased widely due to the belief that natural products are less toxic than conventional medicines. Natural products have been utilised for management of chronic diseases such as diabetes and cancers. Respiratory infections have also been managed using natural products. Allium sativum is one of the natural products that has been utilised in the management of SARS-CoV infections, diabetes and cancer. Methods: This study was aimed at screening bioactive agents in Allium sativum using computational analysis. The targets of the bioactive agents were predicted using SwissTargetPrediction tools. Molecular docking followed, where the docking energies of the bioactive agents to the targets were generated. The bioactive agents were analysed for pharmacokinetics properties using SwissADME as well as toxicity profiles using the ProTox II webserver. The docking scores, toxicities and pharmacokinetics profiles of the bioactive agents in Allium sativum were compared with those of reference compounds. Results: All the bioactives showed lower docking scores than the reference compounds. The bioactives, however, showed some activity on specific receptors such as carbonic anhydrases, cyclooxygenase and ghrelin. All the bioactives showed high gastrointestinal tract absorption and none violated Lipinski’s rule of five. Diallyl trisulphide was predicted to be most lethal, with an LD50 of 100mg/kg, while Alliin was the safest, with 8000mg/kg. Conclusions: In conclusion, bioactives showed lower docking scores than the reference compounds, therefore overall pharmacological activity could be attributed to synergy between the bioactives for a particular receptor.

In this study, a fluorescence polarization immunoassay (FPIA) was developed based on the single-chain variable fragments (scFvs) for fumonisin B_s (FB_s). The scFvs were prepared from FB_s-specific monoclonal antibody secreting hybridomas (4F5 and 4B9). The established FPIA could determine the sum of fumonisin B₁ (FB₁) and fumonisin B₂ (FB₂) within a short time. The IC₅₀ of FPIA for the detection of FB₁ and FB₂ were 29.36 ng/ml and 1,477.82 ng/ml with 4F5 scFv, and 125.16 ng/ml and 30.44 ng/ml with 4B9 scFv, so the 4B9 scFv was selected for detection of FB₁ and FB₂ in maize samples with a limit of detection of 441.54 μg/kg and 344.933 μg/kg. The recoveries ranged from 84.7 to 104.1% with a coefficient of variation less than 14.1% in spiked samples, and the result of the FPIA method was in good consistency with that of HPLC-MS/MS. To supply a better understanding of the immunoassay results, the interactions mechanism of scFvs-FB_s was further revealed by the homology modelling, molecular docking, and molecular dynamic simulation. It was indicated that six complementarity-determining regions (CDRs) were involved in 4B9 scFv recognition, forming a narrow binding cavity, and FB₁/FB₂ could be inserted into this binding cavity stably through strong hydrogen bonds and other interactions. While in 4F5 scFv, only the FB₁ stably inserted in the binding pocket formed by four CDRs through strong hydrogen bonds, and FB₂ did not fit the binding cavity due to the lack of hydroxyl at C10, which is the key recognition site of 4F5 scFv. Also, the binding energy of FB₂-4B9 scFv complex is higher than the FB₂-4F5 scFv complex. This study established a FPIA method with scFv for the detection of FB₁ and FB₁ in maize, and systematically predicted recognition mechanism of FB_s and scFvs, which provided a reference for the better understanding of the immunoassay mechanism.