Hydroxamic acid is a potent moiety not only in the field of cancer therapy but also as a mutagenic agent. Among the various derivatives of hydroxamic acid, SAHA (Suberoylanilide Hydroxamic Acid) is considered as a potent anticancer agent. Scientists from the different corner synthesized different hydroxamic acid moieties with some straight chain oxazole, thiadiazole, biphenyl moieties in the terminal position. Acetylation and deacetylation of histones of the core proteins of nucleosomes in chromatin play an important role in the regulation of gene expression. The level of acetylation of histones is established and maintained by two classes of enzymes, histone acetyltransferase and histone deacetylases, which have been identified as transcriptional coactivators and transcriptional corepressors, respectively. There is increasing evidence that aberrant histone acetylation has been linked to various malignant diseases. Great efforts are currently underway for the design of more potent and less toxic candidates for the treatment of cancer. In recent years, hydroxamic acid derivatives have attracted increasing attention for their potential as highly efficacious in combating various etiological factors associated with cancer. Our main intention to draw an attention is that this single functional moiety has not only fit in the receptor but also create a diversified activity.

Naturally extracted glycosaminoglycan chondroitin sulphate is the reactive product of N-acetylgalactosamine and d-glucuronic acid.

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Background: : T-cell acute lymphoblastic leukemia (T-ALL) is a disease which affects the bone marrow as well as lymphoblast which are expressed on T-cell immune phenotype. Diagnosis of T-ALL patients have shown that the disease presents large tumour burdens and leukemia cells in peripheral blood which often infiltrates into the central nervous system. Objective: Chemotherapy has been used as the main treatment method for this disease but with the recent research on molecular techniques, the studies have shown that NOTCH1 signalling could be a solution to this disease. NOTCH signalling undergoes non regulation in most T-ALL resulting to mutations in NOTCH1. Gamma-secretase (GS) plays a key role of blocking proteolytic activation of NOTCH receptors which could be a therapy for this kind of leukemia. This study thus aims at outlining the role of γ-secretase inhibitor via NOTCH signalling in T-ALL. Result and Conclusion: The role of GSI (γ-secretase inhibitor) in most T-ALL cell lines has been associate with pathway activity of NOTCH signalling. NOTCH1 mutation has however not served as a predictor of γ-secretase inhibitor sensitivity due to a number of factors including gene expression signature of NOTCH pathway activity which does not correlate. Despite the promise of this approach for NOTCH-1 activated T-ALL, not all patients with this condition would be expected to respond. Long-term therapeutic success in cancer is rarely achieved with monotherapy, and even targeting developmental pathways such as NOTCH will most likely require the development of combination regimens. Ultimately, the best use of these new therapeutic targeted agents, may become the next tools of ‘individualized medicine’.

Background: Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase enzyme which controlled the neuronal functions such as neurite outgrowth, synapse formation, neurotransmission, and neurogenesis. The enzyme has two subunits as GSK-3α and GSK-3β. 4ACC, 1Q3D, 3AFG, 1UV5, 1Q5K are the important GSK-3 receptors isolated from Homo sapiens and Mus musculus. This enzyme mainly phosphorylates Tau protein with increased amount in neuronal fibres altogether with beta-amyloid plaques cause neuronal defects like Alzheimer, Parkinson’s and many more. Objective: We investigated the developments of various synthetic GSK-3 inhibitors responsible for the prevention and treatment of neurological disorders like Alzheimer disease, bipolar disorders, antidepressant, neuroprotective etc. Results and Conclusion: It was observed that structures of the GSK-3 inhibitors comprised of benzopyridine, benzthiazole, pyrazole, pyrazine, dioxolo-benzoxazin, oxadiazole, benzimidazole in the skeletal with cyclopropylamide, phenyl carbamothioate, 3-[(propan-2-yl)oxy]propan-1-amine in side chain. The molecules were evaluated against the effectivity of GSK-3, human adenosine kinase, cyclin dependent kinase, and phosphodiesterase-4 along with tail suspension test, forced swim test, percent neuronal survival and other cognitive behaviour. The observations confirmed the remarkable effects of the synthesized molecules to conquer Alzheimer, Parkinson’s depression, psychosis and other forms of neurological disorders.

Purpose: To design and develop a new series of histone deacetylase inhibitors (FP1 -FP12) and evaluate their inhibitory activity against hydroxyacetamide (HDAC) enzyme mixture-derived HeLa cervical carcinoma cell and MCF-7. Methods:The designed molecules (FP1 -FP12) were docked using AUTODOCK 1.4.6. FP3 and FP8 showed higher interaction comparable to the prototypical HDACI. The designed series of 2- (-4H-1,2,4-triazol-5-yl)sulfanyl]-N-hydroxyacetamide derivatives (FP1-FP12) was synthesized by merging 2-[(4-amino-3-phenyl-4H-1, 2, 4-triazol-5-yl) sulfanyl]-N-hydroxyacetamide and 2-{[4-amino-3-(2-hydroxyphenyl)-4H-1,2, 4-triazol-5-yl]sulfanyl}-N hydroxyacetamide derivatives with aromatic substituted oxazolone. The biological activity of the synthesized molecule (FP1-FP12) was evaluated against HDAC enzyme mixture-derived HeLa cervical carcinoma cell and breast cancer cell line (MCF-7).Results: HDAC inhibitory activity of FP10 showed higher IC50 (half-maximal concentration inhibitory activity) of 0.09 μM, whereas standard SAHA molecule showed IC50 of 0.057 μM. On the other hand, FP9 exhibited higher GI50 (50 % of maximal concentration that inhibited cell proliferation) of compared with the standard, adriamycin,