Discovery of novel potent human chondrosarcoma (SW1353) inhibitors: 4-(2/3/4-pyridyl)thiazole 2-acetamide derivatives

• Thank you for your time and effort for the review of our study. Your comments are highly important and we believe that the requested revisions will make the study even better for our readers. We have carefully checked and studied your suggestions. In order for the editorial and reviewers to follow the changes in the manuscript, we have highlighted the changes as ‘yellow’ in the word document. The reviewer response file prepared as ‘point by point’ including answers for all the suggestions. The answers were written in ‘red’ color for the reviewers to follow up the corrections. Chondrosarcoma is the most common cartilage sarcoma among adult patients. It is mainly observed after the degradation of chondrocytes in the case of cell stress. Unfortunately, the mortality among patients is high as a result of metastasis. Here in this study we have discovered some novel 4-(2/3/4-pyridyl)thiazole 2-acetamide derivatives and elucidated their structure using chromatographic and spectroscopic methods. The antitumor activity profile for the synthesized compounds was performed using an MTT assay and apoptotic pathways (BAX, BCL-2) on the chondrosarcoma (SW1353) cell line. Besides, tyrosine kinase activity studies were also performed in order to understand the underlying mechanism of action. Among the synthesized compounds, there are some compounds showed excellent activity on chondrosarcoma cells. Besides, compounds showed no cytotoxicity on healthy fibroblast (L929) cell lines. Among the compounds, the compound having benzimidazole moiety showed the highest activity with IC 50 value of 2.03±1.05 µM compared to doxorubicin (5.05±1.07 µM). The results indicated that the anticancer activity of the compounds might be depending on tyrosine kinase inhibiton. The compounds are also exhibited to induce apoptosis in chondrosarcoma cells. Morphological and colony observations are also successfully visualized.