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The aim of this study was to synthesize a series of novel and known dihydrocarvone-hybrid derivatives (2–9) and to evaluate mycelial growth activity of hybrid molecules against two strains of Monilinia fructicola, as well as their toxicity. Dihydrocarvone-hybrid derivatives have been synthesized under sonication conditions and characterized by FTIR, NMR, and HRMS. Antifungal efficacy against both strains of M. fructicola was determined by half maximal effective concentration (EC50) and toxicity using the brine shrimp lethality test (BSLT). Among the synthesized compounds, 7 and 8 showed the best activity against both strains of M. fructicola with EC50 values of 148.1 and 145.9 µg/mL for strain 1 and 18.1 and 15.7 µg/mL for strain 2, respectively, compared to BC 1000® (commercial organic fungicide) but lower than Mystic® 520 SC. However, these compounds showed low toxicity values, 910 and 890 µg/mL, respectively, compared to Mystic® 520 SC, which was highly toxic. Based on the results, these hybrid compounds could be considered for the development of more active, less toxic, and environmentally friendly antifungal agents against phytopathogenic fungi.

Platelets are the smallest blood cells, and their activation (platelet cohesion or aggregation) at sites of vascular injury is essential for thrombus formation. Since the use of antiplatelet therapy is an unsolved problem, there are now focused and innovative efforts to develop novel antiplatelet compounds. In this context, we assessed the antiplatelet effect of an acylhydroquinone series, synthesized by Fries rearrangement under microwave irradiation, evaluating the effect of diverse acyl chain lengths, their chlorinated derivatives, and their dimethylated derivatives both in the aromatic ring and also the effect of the introduction of a bromine atom at the terminus of the acyl chain. Findings from a primary screening of cytotoxic activity on platelets by lactate dehydrogenase assay identified 19 non-toxic compounds from the 27 acylhydroquinones evaluated. A large number of them showed IC50 values less than 10 µM acting against specific pathways of platelet aggregation. The highest activity was obtained with compound 38, it exhibited sub-micromolar IC50 of 0.98 ± 0.40, 1.10 ± 0.26, 3.98 ± 0.46, 6.79 ± 3.02 and 42.01 ± 3.48 µM against convulxin-, collagen-, TRAP-6-, PMA- and arachidonic acid-induced platelet aggregation, respectively. It also inhibited P-selectin and granulophysin expression. We demonstrated that the antiplatelet mechanism of compound 38 was through a decrease in a central target in human platelet activation as in mitochondrial function, and this could modulate a lower response of platelets to activating agonists. The results of this study show that the chemical space around ortho-carbonyl hydroquinone moiety is a rich source of biologically active compounds, signaling that the acylhydroquinone scaffold has a promising role in antiplatelet drug research.

Since cancer cells have different mitochondrial bioenergetic requirements than non-cancerous cells, therapeutic inhibition of its mitochondrial functionality continues to be an important target for anticancer drug discovery. In this study, a series of acylhydroquinones with different acyl-chain length, and their chlorinated derivatives, in the aromatic ring, synthesized by Fries rearrangement under microwave irradiation, were evaluated for their anticancer activity in two leukemia cell lines. Findings from the primary and secondary screening of the 18 acylhydroquinones, tested at 5 µM on acute promyelocytic leukemia HL-60 and acute lymphoblastic leukemia CEM cells lines, identified an acylchlorohydroquinone (12) with a highly selective anti-proliferative effect toward HL-60 cells. This compound induced S-phase arrest in the cell cycle progression of HL-60 cells with insignificant toxicity on leukemic CEM cells and non-cancerous Hs27 cells. In HL-60 leukemic cells, 12 triggered increased mitochondrial NADH oxidation, increased respiration in presence of oligomycin (state 4o), mitochondrial depolarization, and ROS production, suggesting an uncoupling of OXPHOS. This provoked a metabolic adaptation dependent on AMPK/ACC/autophagy axis, having the mitochondrial β-oxidation a pro-survival role since the combination of 12 and etomoxir, a carnitine palmitoyl-transferase (CPT) inhibitor promoted extensive HL-60 cell death. Finally, 12-induced metabolic stress sensitized to HL-60 cells to cell death by the FDA-approved anti-leukemic drug ABT-199, a BH3 mimetic. Therefore, our results suggest that acylchlorohydroquinone is a promising scaffold in anti-promyelocytic leukemia drug research.

The present study was aimed at evaluating the antibacterial activity of mulinane and azorellane diterpenes isolated from the Andean plants Azorella compacta and A. trifoliolata and semisynthetic derivatives against reference and multidrug-resistant strains. The results revealed that the semisynthetic compound 7-acetoxy-mulin-9,12-diene (5) exhibited antibacterial activity against reference and multidrug-resistant strains of Staphylococcus aureus and moderate antimycobacterial activity against Mycobacterium smegmatis ATCC 14468.

The present study was aimed at evaluating the antibacterial activity of mulinane and azorellane diterpenes isolated from the Andean plants Azorella compacta and A. trifoliolata and semisynthetic derivatives against reference and multidrug-resistant strains. The results revealed that the semisynthetic compound 7-acetoxy-mulin-9,12-diene (5) exhibited antibacterial activity against reference and multidrug-resistant strains of Staphylococcus aureus and moderate antimycobacterial activity against Mycobacterium smegmatis ATCC 14468.

Phytochemical investigation of Azorella madreporica led to the isolation of four known compounds and an unknown chalcone. The structure of the new compound was identified by spectroscopy, including two-dimensional NMR techniques and comparison with published spectral data. The antioxidant activity of chalcone (compound 1) was measured using the 1,2-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay, and the bioactivity was evaluated against five bacteria (Mycobacterium smegmatis ATCC 14468, clinical isolates of Staphylococcus aureus, Klebsiella granulomatis, Morganella morganii and Escherichia coli) and four cancer cell lines. Docking studies with the tested cancer related proteins revealed nearby values of energy between doxorubicin and compound 1. Besides, protein-ligand interactions correlate with these energy values.