1. Department of chemical engineering, Birjand University of technology, Birjand, Iran
Colorectal cancer is the second common cancer in women and the third in men, continues to represent the large cause of mortality in the world. the use of essential oil agents, as one of the main sources of chemopreventive drug, is an extremely promising strategy for cancer prevention. saffron (the dried red stigmas of crocus sativus l. flower) has attracted continuing attention, in addition to its use as a food coloring and flavoring agent, due to treatment of numerous illnesses including cancers. recent studies provided evidence that saffron inhibited the growth of colorectal cancer cells. however anti-colorectal activity of saffron was justified, the investigation on anticancer activity of the saffron phytochemicals is very scarce. the virtual screening of saffron compounds, uses computer-based methods, can simply speed up the search procedure, before a company commits funds to the more expensive screening on actual compounds.
In this work a qsar model is created for the prediction and virtual screening of potent anti-colorectal cancer compounds in saffron against the ht-29 cell line. the constituents of saffron were taken from previous articles. the qsar model was constructed by a data set containing 179 compounds, 86 of them considered as anti-colorectal cancer agents(ic50 <= 0.005 µm) and 93 inactive. for each molecule more than 1000 molecular descriptors were calculated utilizing padel software. the data set was randomly divided into two sets: a training set of 131 compounds for model generation and a test set of 48 compounds for evaluation of the prediction ability of obtained model. in order to virtual screening of compounds in saffron essential oil against the ht-29 cell line, the developed qsar model was used.
The best qsar model with 5 descriptors was developed using the gfa method. this model could correctly classify 131 of 131 compounds (100%) in the training set, while in the prediction set 43 of 48 compounds (89.53%) were correctly classified. with regard to the good quality and predictive power of the developed model, it was used to discovering the potent anti-colorectal cancer constitutes of saffron. the results of classification indicated alpha-isophorone and tetracycloheptane can be considered as anti-colorectal cancer compounds in saffron against the ht-29 cell line.
In this work, a quantitative structure-activity relationship (qsar) model has been developed to virtual screening of anti-colorectal cancer compounds based on a data set of 179 components. high accuracy of developed model indicated it is suitable for discovery of the potent anti-colorectal cancer compounds. therefore it is used for screening the compounds of saffron essential oil and two compounds indicate anti-colorectal cancer activity. however more computational and experimental studies needed to validate these results.