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Malaria is an important global disease that threatened human life. The resistance Plasmodium sp. to the available medicines encourages the search for new antimalarial substances based on new mechanisms on the inhibition of PfMQO (the mitochondrial Plasmodium falciparum enzyme). Objective: The purposes of this study was to screen antimalarial substances from microalgae based on the inhibition of PfMQO. Materials and Methods: Five microalgae were extracted by maceration using chloroform pa and ethanol pa. These ten crude extracts obtained were tested for the inhibitory activity against the PfMQO enzyme. Results: The highest inhibitory activity against PfMQO enzyme was chloroform extract of S. costatum with 91.050% of inhibition and 0.043 µg/mL of IC 50 . The ethanol extract of S. platensis showed 91.999% and 5.25 µg/mL of inhibition and IC 50 , respectively. These results indicated that the two extracts provide high antimalarial activity exceeded a theoretical standard of antimalarial bioactive compounds. Conclusion: Chloroform extract of S. costatum and ethanol extract of S. platensis are promising sources of antimalarial compounds based on the inhibition of PfMQO. SUMMARY ABOUT AUTHORS• Seven samples from a total of ten microalgae extracts (chloroform and ethanol) exhibited high antimalarial activity.• The highest antimalarial activity was shown by the ethanol extract of S. platensis.• Antimalarial activity from S.platensis and S. costatum showed high inhibitory activity of P. falciparum and promising resources to developed antimalarial compounds.

Introduction A combination of chemotherapy agents is the best choice in breast cancer treatment to increase the patient survival rate. 5-fluorouracil (5-FU) is one of the drugs applied in combination with other drugs to control and delay development of cancer cells. Nevertheless, the occurrence of multidrug resistance and dose-limiting cytotoxicity have limited the efficacy of 5-FU treatment. Therefore, the discovery of new anti-breast cancer drugs should be pursued. Objective To study potency of a promising naturally derived compound, caffeic acid phenethyl ester (CAPE), for breast cancer treatment in single and combination with 5-FU. Methods Cytotoxicity of CAPE, 5-FU, and 5-FU+CAPE was studied by in vitro MTT experiment in MCF-7 cell line, and RT-PCR analysis was used to evaluate the change in gene expression due to the treatment. Moreover, an enzymatic assay and molecular docking analysis were applied to evaluate the possible mechanism of substance-induced apoptosis. Results The study revealed that a single treatment of CAPE showed cytotoxicity with IC 50 6.6 ± 1.0 µM and 6.5 ± 2.9 µM at 24 h and 48 h, respectively. Meanwhile, 5-FU showed cytostatic activity. The 5-FU + CAPE has a synergistic effect at 24 h treatment with a CI = 0.5 and an additive effect at 48 h treatment with CI = 1.0. CAPE was also found to enhances the mRNA expression of caspase -8 and BAX within 6 hours in combination with 5-FU compared to 5-FU treatment alone. Our study reveals a new mechanism of CAPE which is related to the inhibition of human dihydroorotate dehydrogenase ( Hs DHODH) with an IC 50 of 120.7 ± 6.8 µM, by bound to the ubiquinone-binding site of the enzyme and could be responsible for inducing extrinsic and intrinsic apoptosis. Conclusion This study demonstrated the cytotoxicity of CAPE potential to induce apoptosis of breast cancer MCF-7 cell line single and cytotoxic–cytostatic combination with 5-FU. Therefore, further studies to develop CAPE and its derivatives will be required to discover new candidates for breast cancer agents.

This study aimed to obtain a microbial active compound as a novel antimalarial drug from Indonesian isolates. Target-based assays were used to screen for antimalarial activity against the parasite mitochondrial, Plasmodium falciparum malate:quinone oxidoreductase (PfMQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against PfMQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by Aspergillus sp. BioMCC f.T.8501 demonstrated stable PfMQO inhibitory activity. Several purification stages, including OCC, TLC, and HPLC, were performed to obtain bioactive compounds from this active extract. All purification steps were followed by an assay against PfMQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited PfMQO activity at IC50 of 51 µM and P. falciparum 3D7 proliferation in vitro at IC50 of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian Aspergillus sp. BioMCC f.T.8501 as a novel inhibitor of PfMQO, which showed inhibitory activity against the proliferation of P. falciparum 3D7 in vitro.