Identifying Potential Autophagy Modulators in Panch Phoron Spices (P5S): An In Silico approach

Despite recent breakthroughs in diagnosis and treatment, cancer remains a worldwide health challenge with high mortality. Autophagy plays a major role in the progression and development. Starving cancer cells obtain nutrients through the upregulation of autophagy. Several compounds derived from natural sources, including animals, plants, and microorganisms, have been identified as potential novel anticancer drugs. Spices play an important role in human health and possess many medicinal properties. Our study aimed to identify potential autophagy modulators from panch phoron spices (P5S) through in silico approaches. Herein, we report a structure-based virtual screening of compounds isolated from P5S (i.e., cumin, fenugreek, fennel, black mustard, and black cumin) against the molecular targets of autophagy. Using various computational tools, we attempted to identify potential modulators of autophagy. Among all the screening results (such as binding energy, hydrogen bonding, drug-likeness, bioactivity, ADME properties, and toxicity), P5S, stigmasterol, and tigogenin showed the best drug-like properties and binding affinity toward the selected targets of autophagy. Furthermore, the stability of both complexes was evaluated by performing a 100 ns molecular dynamics simulation (MDS) using Schrodinger's Desmond Module. Our results provide insight into the efficacy of P5S components against cancer. Therefore, targeting autophagy using these molecules may be an effective and potential drug candidate for cancer treatment. In conclusion, stigmasterol and tigogenin may act as potential candidates for anticancer drugs by targeting autophagy.