Malaria is a prevalent disease threatening worldwide which is affected by Plasmodium parasites. Plasmodium parasites are making resistance gradually which accelerate the innovation of new antimalarial drugs concernment to stand against this disaster extremely. DHFR-TS enzymes are expected target protein which help reproduction of the parasites. Proguanil is a biguanide derivative, most commonly used against of the parasites. According to recent scientific report, malaria parasites are growing strong resistance against proguanil and other anti-malarial drugs constantly. Current study executes to find out the successor bioactive analogues of proguanil on a basis of molecular docking score through in silico analysis which will help to halt the parasites life cycle. AutoDock Vina and Chimera docking tools were used to elucidate the ligand-protein docking and binding interactions. In docking analysis, analogue ZINC16343331 and analogue PubChem CID 10684194 were found to interact with target receptor sites. Using AutoDock Vina and Chimera, binding affinity for analogue ZINC16343331 and PubChem CID: 10684194 were found-7.5 Kcal/mol and 7.3 Kcal/mol respectively, whereas obtained binding energy of proguanil was-6.6 Kcal/mol. Moreover, ZINC16343331 was showing best positive AMES test than proguanil. So, further studies on this analogue could gift the humanity a major breakthrough against the world deadliest disease.