UNAIR NEWS – The world of health has shown a rapid development, including in the pharmaceutical industry. Various efforts to develop new drugs are done in order to get compounds with better effectiveness with low toxicity.
One of the efforts is through a drug design conducted by modifying its structure. Structural modification is done by synthesizing a number of parent compound derivatives by identifying the structure and testing its biological activity. Before the molecular computing test (in silico), the discovery of new drug compounds is long and costly, with possibility of failure.
“The method used is to synthesize compounds by trial and error, then the activity, pharmacokinetic property and toxicity are determined,” Prof. Dr. Suko Hardjono., MS., Apt., UNAIR Faculty of Pharmacy researcher.
In an effort to develop anti-cancer new drug, Prof. Suko and his team predicted the activity of several compounds in silico. These compounds are N-benzoyl-N’-(4-fluoro) phenylthiourea and its four derivatives: N-4- chlorobenzoyl -N’-(4-fluoro) phenylthiourea, N-2,4-diklorobenzoyl-N’-(4-fluoro) phenylthiourea, N-4-bromobenzoyl-N’-(4-fluoro) phenylthiourea and N-4-trifluorometil-benzoyl-N’-(4-fluoro) phenylthiourea with the target enzyme Sirtuin-1.
Prediction of the activity of these compounds is based on the function of the p53 gene. The p53 gene is found in cancer cells and serves to inhibit its proliferation. The function of the p53 gene itself is inhibited by sirtuin-1 enzyme.
“In this study, it is expected that the compound which is predicted to have an activity inhibits the work of the Sirtuin-1 enzyme, so that the function of the p53 gene is not disturbed,” explained Prof. Suko
“The results of the activity prediction show that the five compounds can inhibit the sirtuin-1 enzyme better than hydroxyurea which is still used as an anti-cancer,” he continued.
In addition to predicted its activity, these compounds are also predicted for its pharmacokinetic properties and their toxicity. It is necessary to find out how the drug is absorbed and distributed in the body. Moreover, how drugs are metabolized and excreted from the body must also be considered.
“From this research, the five compounds can be well absorbed in the intestine. Furthermore, they also have no effect on the action of enzymes in the liver that are used to eliminate toxins, “said Prof.Suko.
For toxicity prediction, all compounds do not cause cancer and have low toxicity. From the results of these predictions, it can be concluded that the compound N -4-chlorobenzoyl- N ‘- (4-fluoro) phenylthiourea has good pharmacokinetic properties, the highest activity, and does not cause cancer or interfere with the work of the liver. With these predictions, the compound deserves to be synthesized as a candidate for a new anti-cancer drug. (*)
Author: Sukma Cindra Pratiwi
Editor : Khefti Al Mawalia
Journal paper link:
Hardjoko Suko, Widiandani Tri, Purwanto Bambang T, Nasyanka Anindi L. 2019. Molecular Docking of N-benzoyl-N’-(4-fluorophenyl) thiourea Derivatives as Anticancer Drug Candidate and Their ADMET prediction