IN-SILICO DESIGN, SYNTHESIS AND IN VITRO ANTICANCER AND ANTITUBERCULAR ACTIVITY OF NOVEL AZETIDINONE CONTAINING ISATIN DERIVATIVES
Objective: To design, synthesize and in vitro anticancer and antitubercular evaluation of some new isatin derivatives containing azetidinone.
Methods: Novel azetidinone containing isatin derivatives were designed by using various softwares such as ACD Lab ChemSketch 12.0, Marvin Sketch, Molinspiration, PASS and Schrodinger. The designed molecules having required physico-chemical properties, drug likeness and obeying Lipinskiâ€™s rule of five were selected for the synthesis. These compounds were synthesized by conventional and microwave assisted synthetic methods through a series of three steps. The synthesized compounds were subjected to TLC, melting point determination, IR, 1HNMR and Mass spectroscopic studies. The in vitro anticancer activity of selected compounds was evaluated against MCF7 and L929 by MTT assay method. The antitubercular activity of selected compounds was evaluated by REMA method.
Results: Ten derivatives (AZ-2, AZ-3, AZ-5, AZ-8, AZ-9, AZ-10, AZ-12, AZ-13, AZ-14 and AZ-15) were selected for synthesis with the help of in-silico modeling. In the synthesis, the microwave method took minimum reaction time and gave maximum yield comparing with conventional method. All the synthesized compounds showed characteristic peak in IR, 1HNMR and Mass spectroscopic studies. Based on the Schrodinger Glide XP score, the compounds AZ-13, AZ-5 and AZ-3 were selected for in vitro anticancer and AZ-9, AZ-14 and AZ-3 were selected for antitubercular evaluation. The compound AZ-13 showed significant anticancer activity particularly against L929 cell line and the compound AZ-9 showed significant antitubercular activity comparing with other selected compounds.
Conclusion: These results are useful for further investigation in the future.
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