# Synthetic Transformations and Medicinal Significance of 1,2,3-Thiadiazoles Derivatives: An Update
## 2 Synthetic Approaches
### Anticancer Agents  
Cancer has drawn the attention of today's medical science all over the world because it is the lethal, notably complex, most prominent and serious threat to human health. It forms the lump of uncontrolled growth cells called tumors or neoplasm tumor cells. The neoplasm malignant are diversified heterogeneous cells which have properties of rapid proliferation and capability to invade or spread to other parts of the body through the bloodstream and lymphatic system. Most researchers have devoted their extensive research to developing effective anticancer agents, along with the employment and application of integrated surgical procedures, radiation therapy and chemotherapy [111; 112]. Great advances and many discoveries in the development of a large quantity of anticancer therapeutics such as carboplatin (**105**) cisplatin (**106**) [113; 114; 115], anastrozole (**107**) [116; 117] and doxorubicin (**108**) (Figure 12), etc., have been made over the past 60 years [118; 119; 120; 121]. Noteworthy are the 4,5-diaryl-1,2,3-thiadiazole derivatives obtained by [PERSON] et al. due to their method of synthesis and anticancer properties [122], and results pointed out that compounds **109** and **110** are the lead compounds by exhibiting favorable activity (Figure 13). Growth inhibition rate of tumor cells (obtained from mice S180) by derivative **109** at a dose of 40 mg/kg administrated for 5 days reached 81.0%, while compound **110** displayed a tumor suppression efficacy of 64.2% (at 100 mg/kg of dose administered to mice for five days). These effects were compared with the standard reference CA-4 (combretastatin A-4), which showed a 64.2% antitumor effect at a dose of 40 mg/kg used for  
Figure 11: Antiviral activity of 4-(3,4-dichlorophenyl)-1,2,3-thiadiazole scaffold **104**. Figure 10: 1,2,3-Thiadiazole scaffolds **102** and **103** with anti-TMV activity. 4 days in a mouse model. The SAR study indicated that the reason of the highest antitumor activity of structural motif **109** than reference drug CA-4 and derivative **110** was because of OMe group at C-4 and H at C-3 of 5-phenyl ring of 1,2,3-thiadiazole, while the replacement of hydrogen at C-3 with the nitro group dropped the antitumor activity of derivative **110**. The scaffold **109** could be a promising candidate due to its lower cytotoxicity and excellent antitumor effect [122]. New 1,2,3-thiadiazole derivatives (**111** and **112**; Figure 14) obtained by [PERSON] et al. via Hurd-Mori cyclization were tested against MCF-7 tumor cells. The IC\({}_{50}\) values of compounds **111** and **112** (IC\({}_{50}\) = 12.8 \(\upmu\)g/mL and 8.1 \(\upmu\)g/mL, respectively) were comparable to doxorubicin as the standard anticancer drug with IC\({}_{50}\) = 3.13 \(\upmu\)g/mL. The derivative **111** showed the highest anti-breast cancer activity than the scaffold **112** and reference drug doxorubicin [123]. [PERSON] et al. reported the synthetic protocol to achieve the substituted 4,5-diaryl-1,2,3-thiadiazoles as Hsp90 chaperone protein inhibitors. This protein plays a significant part in developing tumor cells, so its inhibition is the main target of many anticancer drugs. The Hsp90 chaperone stabilizes a number of proteins that are essential for the growth of tumors, due to which researchers all over the world are interested in the development of Hsp90 inhibitors which would be investigated as anticancer agents. In the group of tested  
Figure 14: Anticancer activity of 2-thioamide-1,2,3-thiadiazole **111** and **112**. Figure 12: Clinical anticancer drugs **105–108**. Figure 13: Antitumor effect of 1,2,3-thiadiales **109** and **110**. derivatives, structure **113** deserves special attention as an inhibitor of cancer cells with GI\({}_{50}\) value of 0.69 uM for U2 OS (osteosarcoma) cells and 0.70 uM for HeLa (cervical carcinoma) cells (Figure 15) [124]. Isothermal titration calorimetry was used to determine the binding affinity of compound (113) to Hsp90F and Hsp90N.