Studying the Cytotoxic Activity of Newly Designed and Synthesized HDAC Inhibitors Derivatives of Pentanoyl Anilide‐5‐Biguanide

Histone deacetylase inhibitors (HDAC‐Is) have suggested to be a promising class of anticancer agents that are used for many types of cancer and they are proposed to be new treatment for breast cancer (BC) management. Histone deacetylase enzymes (HDAC) play an important role in BC development and progression where found to be overexpressed in the cancer cells, therefore the inhibition of these enzymes may be the key to develop new anticancer agents against BC. The study aims to synthesize three newly designed molecules derived from fusion of acylanilide part of well‐known HDAC inhibitor vorinostat with the biguanide part of metformin to get molecules are synthesized successfully as follows: pentanoyl anilide‐5‐biguanide (12), pentanoyl para‐fluoroanilide‐5‐biguanide (13), and pentanoyl para‐chloroanilide‐5‐biguanide (14). The in silico study using docking programs, SeeSAR and Chimera programs, to find and assess the inhibitory effect of these analogues against HDAC enzymes (HDAC1, 2, and 3) is deducted. Then, the practical synthesis, purification, and identification are performed. The determination of cytotoxicity for these newly synthesized analogues against MCF‐7 cell line of BC is done through MTT stain method. The results obtained reveal considerable inhibition of cancer growth with IC50 range 78.95–99.18 µM. These newly synthesized analogues may be represented as promising line for the discovery of new agents fighting BC in addition to other types of cancer.