अमूर्त

Virtual screening for novel inhibitors of human histone deacetylase 6: Promising new leads for oral squamous cell carcinoma.

Sandhya Vijayasarathy

Over 90% of Oral Cancers are Oral Squamous cell carcinomas and is the most common form of cancer of head and neck. The incidence and morbidity rate of Oral Cancer is increasing worldwide. Although treatment modalities have advanced, the survival rate of oral cancer patients has not improved significantly over the years. Thus, there arises a need for identification of new drug targets besides development of new and effective drugs for this disease. Histone Deacetylase 6 (HDAC6), a class IIB member of HDAC family, is known to be upregulated in this disease in addition to being associated with tumor growth. Thus, HDAC6 could be a promising drug target for this disease. In this study, structure-based virtual screening was used to screen a library of 1539 natural compounds from NPACT (Naturally Occurring Plant based Anti-cancerous Compound-Activity-Target Database). Upon filtering and docking, top 30 hits were identified and two of them namely Camptothecin and Diosgenin were tested experimentally on oral squamous cell carcinoma cell lines for anti-proliferative effect. It was found that both these compounds exhibited inhibitory activity against the cancerous cells, thus validating our findings. Moreover, from virtual screening results, it was observed that top 29 hits namely Subtrifloralactone A, Diosgenin, Inophyllum E, Taiwanin E, Camptothecin and many others showed better binding energy than the standard HDAC inhibitor (Vorinostat), thus signifying that these compounds can be potential inhibitors of HDAC6 thus serving as promising leads for Oral Squamous Cell Carcinoma