Synthesis, In Silico and In Vivo Evaluation of Novel 1, 3, 4-Thiadiazole Analogues as Novel Anticancer Agents

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Author(s): Byran Gowramma*, Swathi Krishna, Manal Mohammed, Thaggikuppe K Praveen, Rajagopal Kalirajan, L Kaviarasan.

Journal Name: Letters in Drug Design & Discovery

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Abstract:

The synthesis of 2-Amino naphthoxy-1, 3, 4-thiadiazole / 5-(1, 3-benzodioxol-5-yl)-1, 3, 4-thiadiazol-2-amine an intermediate were carried out by cyclization method. In the current study a mixture of thiosemicarbazide and naphthoxyacetic acid / piperonylic acid and phosphoryl chloride was subjected to cyclization using phosphorous oxy chloride to get 2-aminonaphthoxy-1, 3, 4-thiadiazole (1) / 5-(1, 3-benzodioxol-5-yl)-1, 3, 4-thiadiazol-2-amine (3). Futher compound (1) was reacted with different aromatic aldehydes in methanol to form (Z)-N-{5-[(naphthalen-2-yloxy) methyl] -1, 3, 4-thiadiazol-2-yl}-1 substituted aromatic aldehyde methanimine (2a-e) / (Z)-N-[5-(1, 3-benzodioxol-5-yl)-1,3,4-thiadiazol-2-yl]-1-( substituted aromatic aldehydes) methanimine (4a-e). The above derived synthesized compounds were confirmed through their melting point, IR, 1H-NMR and Mass spectrum studies, and later evaluated for their anticancer activity. The docking study was carried out by Discovery studio 4.1 (Accelrys) software against DNA-binding domain of STAT3. The docking result showed that all compound have significant docking score against targeted enzyme. From the in-vivo anticancer studies it was observed that the synthesized compound 4a and 4d were showing very good anti-cancer activity which is comparable to standard drug, while the rest of the compounds were found to be mild in their potency for anticancer studies.

Keywords: 1, 3, 4-Thiadiazole, Characterization, docking, Discovery studio , in-vivo anti-cancer activity

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1570180816666190710145939
Price: $95