In silico Strategy: A Promising Implement in the Development of Multitarget Drugs against Neurodegenerative Diseases.

Multi-target drug development (MTDD) is the demand of the recent era, especially in the case of multi-factorial conditions such as cancer, depression, neurodegenerative diseases (NDs), etc. The MTDD approaches have many advantages; avoidance of drug-drug interactions, predictable pharmacokinetic profile, and less drug resistance. The wet lab practice in MTDD is very challenging for the researchers, and the chances of late-stage failure are obvious. Identification of an appropriate target (Target fishing) is another challenging task in the development of multi-target drugs. The in silico tools will be one of the promising tools in the MTDD for the NDs. Therefore the outlook of the review comprises a short description of NDs, target associated with different NDs, in silico studies so far done for MTDD for various NDs. The main thrust of this review is to explore the present and future aspects of in silico tools used in MTDD for different NDs in combating the challenge of drug development and the application of various in silico tools to solve the problem of target fishing.

1,3,4-Oxadiazole: An Emerging Scaffold to Inhibit the Thymidine Phosphorylase as an Anticancer Agent.

Thymidine phosphorylase (TP), also referred to as "platelet-derived endothelial cell growth factor" is crucial to the pyrimidine salvage pathway. TP reversibly transforms thymidine into thymine and 2-deoxy-D-ribose-1-phosphate (dRib-1-P), which further degraded to 2-Deoxy-D-ribose (2DDR), which has both angiogenic and chemotactic activity. In several types of human cancer such as breast and colorectal malignancies, TP is abundantly expressed in response to biological disturbances like hypoxia, acidosis, chemotherapy, and radiation therapy. TP overexpression is highly associated with angiogenic factors such as vascular endothelial growth factor (VEGF), interleukins (ILs), matrix metalloproteases (MMPs), etc., which accelerate tumorigenesis, invasion, metastasis, immune response evasion, and resistant to apoptosis. Hence, TP is recognized as a key target for the development of new anticancer drugs. Heterocycles are the primary structural element of most chemotherapeutics. Even 75% of nitrogen-containing heterocyclic compounds are contributing to the pharmaceutical world. To create the bioactive molecule, medicinal chemists are concentrating on nitrogen-containing heterocyclic compounds such as pyrrole, pyrrolidine, pyridine, imidazole, pyrimidines, pyrazole, indole, quinoline, oxadiazole, benzimidazole, etc. The Oxadiazole motif stands out among all of them due to its enormous significance in medicinal chemistry. The main thrust area of this review is to explore the synthesis, SAR, and the significant role of 1,3,4-oxadiazole derivatives as a TP inhibitor for their chemotherapeutic effects.