Multicomponent access to novel proline/cyclized cysteine tethered monastrol conjugates as potential anticancer agents

The versatility of multicomponent Biginelli’s reaction is exploited in the development of proline and cyclized cysteine tethered conjugates of monastrol, a kinesin Eg5 inhibitor. Ten new conjugates are synthesized focusing on structural replacement of the ester moiety (C-5 position) of the monastrol backbone with amino acid based amide moieties. On cytotoxic evaluation, conjugate 24 has shown promising in vitro cytotoxic activity against leukemia. Molecular docking studies revealed that the conjugates 19 and 24 exhibit better interaction at kinesin Eg5 receptor compared to monastrol. Moreover, computational calculations and predictions of important molecular properties suggest that these new amino acid based conjugates could be further improved to provide potential anticancer agents. Keywords: Monastrol, Amino acids, Multicomponent Biginelli’s reaction, Anticancer agents, Docking studie

Anti-tubercular agents. Part 6: Synthesis and antimycobacterial activity of novel arylsulfonamido conjugated oxazolidinones

As a part of investigation of new anti-tubercular agents in this laboratory, herein we describe the synthesis of a newclass of arylsulfonamido conjugated oxazolidinones. The in vitro activity of these conjugated (6aef,7aed, 9aec and 11aec) molecules against Mycobacterium tuberculosis H37Rv by using rifampicin and linezolide as positive controls is discussed, compounds 7c and 9aec are found to be the most active members in this series. Further, cytotoxicity of the potent conjugates of the series (7c, and 9aec) was evaluated on human foreskin fibroblast (HFF) cells by using MTT assay. Finally, these studies suggest that compounds 7c and 9a mayserve as promising lead scaffolds for further generation of newas anti-TB agents

Anti-tubercular agents. Part 5: Synthesis and biological evaluation of benzothiadiazine 1,1-dioxide based congeners

In an effort to discover new and effective chemotherapeutic agents from this laboratory for the treatment of tuberculosis, here in we describe the synthesis and biological evaluation of a series of novel benzothiadiazine 1,1-dioxide (BTD) based congeners by using rifampicin, streptomycin; ciprofloxacin and amphotericin as positive controls. Further, to understand structural requirements for exploring the structure activity relationship of BTDs, cytotoxicity and in vivo study of recently reported potent molecule 4 (MIC ¼ 1 mg/mL) is also discussed