Heat shock proteins (HSPs) and histone deacetylase 6 (HDAC6) are induced under oxidative stress, which promotes oncogenesis. HSPs are regulated by heat shock factor1 (HSF1). HDAC6, a class IIb deacetylase, plays an essential role in tumorigenesis and cell stress response. HSPs, HSF1 and HDAC6 are up-regulated in cancer. In the present study, we explored the effect of curcumin, a phytochemical, on HSPs (27, 70, 90), HSF1 and HDAC6 in two different leukemia cell lines (K-562 and HL-60). The association between HDAC6, HSPs, and intrinsic oxidative stress was also investigated. Overexpression of HSPs (27, 70, 90), HSF1, and HDAC6 in leukemia cells were down-regulated by curcumin, and the effects on HSPs 27and 70 were less than that on HSP 90. This resulted in cell cycle arrest at the G2/M stage, leading to apoptosis. Different cell cycle regulatory proteins (p53, p21, cyclin B1, CDK1, Cdc25C) and some apoptosis-related proteins (Bcl-2, Bax, Bid, Bad, Apaf1, AIF and Cyt c) were altered by curcumin. Increased ROS levels in leukemia cells were quenched by curcumin. A probable association between high ROS level and the overexpression of the tumor markers was established in this study. Thus, curcumin enhanced the efficacy of anti-tumor drugs imatinib-mesylate and cytarabine through the inhibition of the tumor markers.

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Computer-aided drug design (CADD) depends on the extent of structure and other information available regarding the target (enzyme/receptor/protein) and the ligands. The theoretical basis of CADD involves molecular mechanics, quantum mechanics, molecular dynamics, structure-based drug design (SBDD), ligand-based drug design (LBDD), homology modeling, ligplot analysis, molecular docking, de novo drug design, pharmacophore modeling and mapping, virtual screening (VS), quantitative structure-activity relationships (QSARs), In silico ADMET (absorption, distribution, metabolism, excretion and toxicity) prediction etc. CADD centre was created to foster collaborative research between biologist, biophysicists, structural biologists and computational scientists. The major goal of the CADD centre is to initiate these collaborations leading to the establishment of research projects to discover novel chemical entities with the potential to be developed into novel therapeutic agents.

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