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.