In the present study there is a brief literature review covering the most important biological activities and the general methods for synthesis of pyridine derivatives. In the present work, Novel class of pyridine derivatives were prepared starting from Ethyl 4-(nicotinamido)benzoate III, which is obtained from reaction of ethyl 4-aminobenzoate with 1-nicotinoyl benzotriazole. The reaction of compound III with hydrazine hydrate yielded acid hydrazide IV. This acid hydrazide was utilized in the synthesis of several hydrazones Va-s and VIa-d by reaction with different aldehydes and aldoses, respectively. (Scheme1) In addition, oxadiazole VII was obtained by refluxing acid hydrazide IV with carbon disulfide and potassium hydroxide in ethanol. Alkylation of oxadiazole VII with various alkylating agent yielded compounds VIIIa-c, IXa-i and Xa-i. (Scheme2) On the other hand, triazole XII was synthesized by conversion of acid hydrazide IV to potassium dithiocarbazinate XI as intermediate through stirring of acid hydrazide IV with carbon disulfide in potassium hydroxide in ethanol which further refluxed with excess of hydrazine hydrate in dioxane. Further alkylation of triazole XII with appropriate alkylating agents gave compounds XIIIa,b and XIVa-g. Refluxing of triazole XII with different aldehyde produced compound XVa-c. (Scheme3) Furthermore, theoretical discussion and detailed survey for the experimental results attained with interpretation of data. The chemical structure of the newely synthesized compounds was confirmed by IR, 1HNMR, 13CNMR, mass spectrometry and elemental analysis. All of the newly synthesized pyridine derivatives were screened for their anticancer activities. Compounds Va-s were tested for their inhibitory activities against pan HDACs (contains predominantly HDAC1 and HDAC2 isozymes) and against HDAC3 isoform. Among these, compounds Vb and Vn showed comparable pan HDAC inhibitory activity (IC50 = 4.648 μM and IC50 = 5.481 μM respectively) compared with BG45 (IC50 = 5.506 μM). Compound Vb exhibited the best potency against HDAC3 with IC50 = 0.694 μM. In addition, the anti-proliferative activity of the synthesized compounds Va-s was evaluated against three different cancer cell lines including B16F10, MCF-7, and A549. Compound Vb displayed the highest anti-proliferative potency (IC50 = 4.66 μM in B16F10 cell line) and compounds Vb, Vc, Vh, Vi, Vl, Vm, and Vn exhibited higher cytotoxicity against all cell lines compared with the reference BG45. The selected potent compounds also displayed significant selectivity against cancer cell lines over normal human embryonic kidney (HEK-293) cell line. Molecular modelling study displayed possible interactions between the most potent inhibitor Vb and HDAC3 active sites