We have synthesized 24 1,4-dihydropyridine compounds (1,4-DHPs) with different substituents at the aromatic ring by microwave-assisted one-pot Hantzsch multicomponent reaction and evaluated their in vitro activities against Toxoplasma gondii and Leishmania major. We have found that compound 9 ((±)-ethyl 2,7,7-trimethyl-4-(2-nitrophenyl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) is active against L. major amastigotes (IC50 = 10.6 μM), but it is poorly selective for L. major over Vero cells (SI = 1.13) and macrophages (SI = 0.42). Among the evaluated 1,4-DHPs, compound 4 ((±)-ethyl 4-(4-(benzyloxy)­phenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate) is the most active against T. gondii, providing the lowest IC50 (3.1 μM) and the highest selectivity for this parasite (SI = 5.57) over Vero cells. Docking studies revealed that compound 4 has a high affinity for the T. gondii target (PDB ID: 4JBV). Furthermore, ADME-T predictions indicated that compound 4 meets the drug-likeness criteria without violating any Lipinski, Veger, or Egan’s rules.

Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N-methyl-4-piperidone-derived monoketone curcuminoids (MKCs) against Candida albicans, C. krusei, and a representative panel of cariogenic bacteria was assessed. Methods: Fifteen MKCs were synthesized using an environmentally friendly base-catalyzed Claisen–Schmidt condensation between an aromatic aldehyde (R-PhCHO) and N-methyl-4-piperidone ethanol using NaOH as the catalyst. These compounds were evaluated for their antibacterial activity against a representative panel of cariogenic bacteria, along with their antifungal activity against Candida krusei and C. albicans. The antimicrobial activity was determined based on the Minimum Inhibitory Concentration (MIC) values. Results: Most of the compounds were obtained in about 2 h in yields ranging from 40 to 70%. None of the compounds displayed antifungal activity, even at 100 μg/mL, the highest tested concentration. Similarly, none of the compounds were active against Enterococcus faecalis. On the other hand, compounds 1 (R = H), 10 (R = 3,4,5-OMe), and 13 (R = 3-F) displayed moderate activity against Streptococcus mutans (13), S. salivarus (1), L. paracasei (1 and 10), S. mitis (1, 10, and 13), S. sanguinis (1, 10, and 13), and S. sobrinus (13), with MIC values of 250 μg/mL and 500 μg/mL. The presence of the N-methyl-4-piperidone ring was found to boost the antibacterial activity as compared to the corresponding acetone-derived MKCs. Moreover, the antibacterial activity of compounds 10 and 13 was associated with the presence and position of the fluor atom and the methoxy groups at the aromatic ring. Conclusions: This study contributed to a better understanding of the antimicrobial activity of MKCs, whose data in the literature are still scarce.

Background/Objectives: Recent reports have demonstrated the antiparasitic activity of 1,4-dihydropyridine (1,4-DHPs). This study aimed to assess the in vitro antischistosomal activity of 24 1,4-DHPs against Schistosoma mansoni adult worms. Methods: Sixteen hexahydroquinolines (1–16) and eight Hantzsch esters (17–24) previously obtained through a multicomponent Hantzsch reaction were tested in vitro against Schistosoma mansoni adult worms. In silico studies with the most active compounds were also carried out. Results: Among the tested compounds, the Hantzsch esters 20 (diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) and 21 (diethyl 4-(3-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) provided the lowest IC₅₀ (15.2 and 13.1 µM, respectively) and the highest selectivity for this parasite (SI = 2.31 and >4.59, respectively). Conclusions: Docking studies revealed that compound 21 has a high affinity for the S. mansoni target (PDB ID: 6UY4). Furthermore, ADMET predictions indicated that compound 21 meets the drug-likeness criteria without violating any Lipinski, Veber, or Egan’s rules.

Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N-methyl-4-piperidone-derived monoketone curcuminoids (MKCs) against Candida albicans, C. krusei, and a representative panel of cariogenic bac-teria was assessed. Methods: Fifteen MKCs were synthesized using an environmentally friendly base-catalyzed Claisen-Schmidt condensation between an aromatic aldehyde (R-PhCHO) and N-methyl-4-piperidone ethanol us-ing NaOH as the catalyst. These compounds were evaluated for their antibacterial activity against a representative panel of cariogenic bacteria, along with their antifungal activity against Candida krusei and C. albicans. The antimi-crobial activity was determined based on the Minimum Inhibitory Concentration (MIC) values. Results: Most of the compounds were obtained in about 2 hours in yields ranging from 40 to 70%. None of the compounds displayed antifungal activity, even at 100 µg/mL, the highest tested concentration. Similarly, none of the compounds were active against Enterococcus faecalis. On the other hand, compounds 1 (R=H), 10 (R=3,4,5-OMe), and 13 (R=3-F) dis-played moderate activity against Streptococcus mutans (13), S. salivarus (1), L. paracasei (1 and 10), S. mitis (1, 10, and 13), S. sanguinis (1, 10, and 13), and S. sobrinus (13), with MIC values of 250 µg/mL and 500 µg/mL. The presence of the N-methyl-4-piperidone ring was found to boost the antibacterial activity as compared to the corresponding acetone-derived MKCs. Moreover, the antibacterial activity of compounds 10 and 13 was associated with the pres-ence and position of the fluor atom and the methoxy groups at the aromatic ring. Conclusions: This study contrib-uted to a better understanding of the antimicrobial activity of MKCs, whose data in the literature are still scarce.

Chemical compositions of essential oils (EOs) from Pelargonium graveolens (EO-PG), Lavandula angustifolia (EO-LA) and Cananga odorata (EO-CO) flowers were determined by GC-MS and GC-FID. Antibacterial activities were determined by the microdilution broth method in 96-well culture plates and MIC and MBC values were expressed as mg/mL. EOs were assayed individually and showed to be active against Xanthomonas citri, X. euvesicatoria, X. vasicola, X. campestris, Pseudomonas fluorescens, Xylella fastidiosa, Burkholderia cepacia, Pantoea ananatis, Pectobacterium carotovorum and Ralstonia solanacearum at concentrations between 0.31 and 10 mg/mL. Blend 2 (EO-PG: EO-LA: EO-CO 3:1:1), out of the three blends prepared by this study, was the most promising one since it exhibited the lowest values of MIC and MBC, i.e., between 0.31 and 1 mg/mL. In short, this study showed, for the first time, that EOs and their blends may be promising tools in agricultural defense to prevent severe bacterial diseases in plants.

Background/Objectives: Leishmaniasis and toxoplasmosis are zoonoses that cause millions of deaths annually. This study aimed to synthesize and investigate the in vitro antileishmanial and antitoxoplasmal activity of eight ace-tone-derived monoketone curcuminoids (MKCs). Methods: MKCs 1-8 were synthesized using a base-catalyzed Claisen-Schmidt condensation. These compounds were evaluated against Leishmania major promastigotes and amastigotes, and Toxoplasma gondii. Results: Compounds 4 ((1E,4E)-1,5-bis(4-chlorophenyl)penta-1,4-dien-3-one) and 5 ((1E,4E)-1,5-bis(4-bromophenyl)penta-1,4-dien-3-one) were very active against L. major promastigotes (IC50 of 6.9 and 6.6 µM, respectively) and amastigotes (IC50 of 21.4 and 30.3 µM, respectively). Compound 4 was also active against T. gondii (IC50 = 15.8 µM). Docking studies revealed that compounds 4 and 5 has a high affinity for the L. major target (PDB ID: 1E92). Conclusions: The results of this study indicated that the presence of halogen (chlorine or bromine) atoms boosts the antileishmanial and antitoxoplasmal activity of acetone-derived monoketone curcuminoids. Furthermore, ADMET predictions indicated that compounds 4 and 5 meets the drug-likeness criteria without violating any Lipinski, Veger, or Egan’s rules