Abstract Cytosporones, a class of octaketide resorcinolic lipids, have drawn the attention of researchers for exhibiting a number of notable biological properties. Herein, we describe routes to synthesize the bioactive synthetic resorcinolic lipids AMS35AA and AMS35BB with excellent overall yields using 3,5-dimethoxybenzoic acid as the starting material. The methods proved remarkably efficient to achieve the target compounds and comprise the synthesis of AMS35AA catalyzed by ascorbic acid (vitamin C).

Natural and synthetic sulfur-bearing organic compounds have many applications in medicinal chemistry. This article reports the preparation of amphiphilic β-hydroxy sulfides, sulfoxides, and sulfones derived from cardanol and glycerol. Thiolysis of cardanol epoxide 3 with various thiols (4a-4j) in ethanol or water yielded the corresponding β-hydroxy sulfides 5a-5j (61-95%). Treatment with 30% H2O2 in acetic acid at ambient temperature completely converted these products into β-hydroxy sulfoxides 6a-6j and sulfones 7a, 7c-7f, 7h-7j. The synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, high-resolution mass spectroscopy (HRMS) and performed the in vitro evaluation antimicrobial activities against standard strains of Staphylococcus aureus and Escherichia coli. Compounds 5a, 5d-5f, and 5h-5j proved moderately active against S. aureus. None of the compounds were active against E. coli. β-Hydroxy-sulfides 5a-5j were also evaluated for antioxidant properties but failed to exhibit significant activity.

The synthesis of novel amino alcohol derivatives based on cardanol and glycerol were achieved in good yields and characterized by 1H and 13C NMR (nuclear magnetic resonance) and MS (mass spectrometry). In addition, we evaluated the in vitro antimicrobial activity against Gram-positive (Staphylococcus aureus, standard and clinical strains), Gram-negative (Escherichia coli) and M. tuberculosis bacterial strains. The bioassay results indicated that four compounds showed activity against S. aureus, including the clinical resistant strain, with MIC (minimum inhibitory concentration) ranging from 3.90 to 15.60 µg mL-1 and M. tuberculosis, with MIC90 (minimum inhibitory concentration required to inhibit the growth of 90% of organisms) ranging from 3.18 to 7.36 µg mL-1.

Abstract The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment.

Abstract Chemotherapy is one of the major approaches for the treatment of cancer. Therefore, the development of new chemotherapy drugs is an important aspect of medicinal chemistry. Chemotherapeutic agents include isocoumarins, which are privileged structures with potential antitumoral activity. Herein, a new 3-substituted isocoumarin was synthesized from 2-iodo-3,5-dimethoxy-benzoic acid and oct-1-yne in a cross-coupling Sonogashira reaction followed by a copper iodide-catalyzed intramolecular cyclization as key step using MeOH/Et3N as the solvent system. The present study also evaluated the leukometry, phagocytic activity, genotoxic potential and cell death induction of three different doses (5 mg/kg, 10 mg/kg and 20 mg/kg) of this newly synthesized isocoumarin, alone and in combination with the commercial chemotherapeutic agents cyclophosphamide (100 mg/kg) and cisplatin (6 mg/kg) in male Swiss mice. The results suggest that the isocoumarin has genotoxicity and causes cell death. Noteworthy, this new compound can increase splenic phagocytosis and lymphocyte frequency, which are related to immunomodulatory activity. When combined with either cyclophosphamide or cisplatin, chemopreventive activity led to a reduction in the effects of both chemotherapeutic drugs. Thus, the new isocoumarin is not a candidate for chemotherapeutic adjuvant in treatments using cyclophosphamide or cisplatin. Nevertheless, the compound itself is an important prototype for the development of new antitumor drugs.

ABSTRACT Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins. These derivatives were tested for toxicity against Aedes aegypti larvae. The results showed that iodohydrins are very promising compounds for making commercial products to combat the vector mosquito larvae presenting a LC50 of 0.0023 ppm after 72 h of exposure.

Abstract Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide.

Octocrylene (2-ethylhexyl 2-cyano-3,3-diphenyl-2-propenoate) is present in several sunscreens and is known to work synergistically with UV filters. We prepared eight octocrylene-related compounds to test their photoprotective activities by measuring diffuse transmittance. The compounds had varied photoprotection profiles, with Sun Protection Factors (SPF) ranging from 1 to 5 and UVA Protection Factors (UVAPF) ranging from 1 to 8. Compounds 4, 5, and 7 showed the best protection against UVB sunrays, while compounds 5, 6, and 7 presented the best results for protection from UVA, so compound 7 had the most balanced protection overall. Results for compounds 4, 8, and 9 are reported for the first time in the literature.

We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15).

A busca por herbicidas eficientes e ambientalmente corretos tem sido foco de numerosos estudos sobre a síntese de compostos isolados de fontes naturais. Citosporonas, as quais são lipídeos fenólicos isolados de fungos, apresentam notáveis propriedades biológicas. Este artigo relata a preparação das citosporonas A, B e C, através de uma rota sintética curta e com excelentes rendimentos. Os compostos sintetizados foram avaliados quanto às suas atividades alelopáticas em sementes de alface (Lactuca sativa L). Citosporona A e seu precursor metilado mostraram notável atividade alelopática, inibindo a germinação de sementes e crescimento das plântulas.

The search for efficient, environmentally friendly herbicides has been the focus of numerous studies on the organic synthesis of compounds isolated from natural sources. Cytosporones, which are phenolic lipids isolated from fungi, exhibit noteworthy biological properties. This paper reports the preparation of cytosporones A-C from the same starting material through a short synthetic route, with good yields. All compounds were tested for allelopathic activity on lettuce (Lactuca sativa L) seeds. Cytosporone A and its methylated precursor showed remarkable allelopathic activity, inhibiting seed germination and plantule growth.

Presently glycerol is considered a co-product of biodiesel industry. As the biodiesel production is exponentially increasing, glycerol generated from the transesterification of vegetable oils and fats is also being produced on a large scale, and turned out to be essential seeking for novel alternatives to the consumption of the extra volume, in crude and/or as derivatives high added value. This review mainly deals with chemical and enzymatic transformations of glycerol to obtain chiral building blocks for synthesis of pharmaceuticals and natural products.

A series of 15 ω-aminoalkoxylxanthones containing methyl, ethyl, propyl, tert-butylamino and piperidinyl moieties were synthesized from a natural xanthone isolated from a lichen species. These compounds were tested for their in vitro antibacterial properties against Gram-positive and Gram-negative bacteria and cytotoxicity against a number of human tumor cell lines was too evaluated. The newly synthesized derivatives revealed selective activity against Staphylococcus aureus (Gram-positive), and the most promising results are for a multidrug resistant strain, for which six of these compounds showed good activity (MICs 4 µg/mL). Many derivatives inhibited tumor cells growth and most compounds were active on multiple lines.

The electrochemical behavior of the interaction of amodiaquine with DNA on a carbon paste electrode was studied using voltametric techniques. In an acid medium, an electroactive adduct is formed when amodiaquine interacts with DNA. The anodic peak is dependent on pH, scan rate and the concentration of the pharmaceutical. Adduct formation is irreversible in nature, and preferentially occurs by interaction of the amodiaquine with the guanine group. Theoretical calculations for optimization of geometry, and DFT analyses and on the electrostatic potential map (EPM), were used in the investigation of adduct formation between amodiaquine and DNA.

Neste trabalho avaliou-se a capacidade de biotransformação do aduto de Diels-Alder triciclo[6.2.1.0(2-7)]undeca-4,9-dien-3,6-diona (1) e dois derivados sintéticos pelo fungo sapróbio Mucor ramosissimus Samutsevitsch. Produtos de oxidação, isomerização e redução regiosseletiva e enantiosseletiva foram obtidos.

The present study aimed to evaluate the ability for biotransformation of the Diels-Alder adduct tricyclo[6.2.1.0(2,7)]undeca-4,9-dien-3,6-dione (1) and two synthetic derivatives by the saprobe fungus Mucor ramosissimus Samutsevitsch. Products from oxidation, isomerization and, regioselective and enantioselective reduction were achieved.

Inspired by the structure and biological activities of resorcinolic lipids and, particularly cytosporone A- a potent inhibitor of plantule germination and growth, we have performed the synthesis of the analogs 3-heptyl-3-hydroxy-5,7-dimethoxy-2-benzofuran-1(3H)-one (1) and 3-heptyl-3-hydroxy-4,6-dimethoxy-2-benzofuran-1(3H)-one (2). The intermediates and products were submitted to allelopathic test using Lactuca sativa L. seeds. Target compound 1 showed an inhibitory effect on germination and growth of hypocotyl and radicle in milimolar range.