Accessing Promising Passerini Adducts in Anticancer Drug Design.

The 3-component Passerini reaction (3CPR), discovered little more than 100 years ago, has been demonstrated in the last few decades to be a valuable tool for accessing structural diversity and complexity, essential topics to consider in drug discovery programs. Focusing on accessing a fine-tuned family of α-acyloxyamide-oxindole hybrids, we underline herein our latest insights regarding the use of this mild reaction approach to obtain promising anticancer agents. Cheap and commercially available isatin was used as starting material.

Chemical Composition, Enantiomeric Distribution, and Physical Properties of the Fruit Essential Oil from (Reynel) Rutaceae from Ecuador.

The essential oil was obtained by steam distillation, using a Clevenger apparatus, from the pericarp of the fruit of from Ecuador. The qualitative and quantitative analyses were performed by gas chromatography coupled with mass spectrometry (GC-MS) and flame ionization detection (GC-FID) on two capillary columns with non-polar DB-5ms and a polar HP-INNOWax stationary phase. Thirty-three components were identified, accounting for 99.

Staurosporine as a Potential Treatment for Keratitis Using Mouse Cornea as an Ex Vivo Model.

is a ubiquitous genus of amoebae that can trigger a severe and progressive ocular disease known as Keratitis (AK). Furthermore, current treatment protocols are based on the combination of different compounds that are not fully effective. Therefore, an urgent need to find new compounds to treat infections is clear.

Novel Coumarin-Steroid/Terpenoid Hybrids: In Vitro and In Silico Anticancer Studies.

We have synthesized a series of novel coumarin-steroid and triterpenoid hybrids and evaluated their potential anticancer activity through molecular docking calculations and in vitro antiproliferative assays. These hybrids, derived from estrone and oleanolic acid, were linked via hydrocarbon spacers of varying lengths. Molecular docking studies against human aromatase revealed strong interactions, particularly for compound 11d, which exhibited significant binding affinity (-12.

Novel tetrahydropyran-triazole hybrids with antiproliferative activity against human tumor cells.

A series of new hybrid compounds was prepared combining tetrahydropyran rings with different aromatic systems by means of a 1,2,3-triazole, using a building block strategy. The design of these structures was guided by Lead-Likeness and Molecular Analysis (LLAMA) software, adding modifications to our most potent scaffold (the tetrahydropyran ring) to generate promising "lead-like" candidates, which were subsequently compared against reported anticancer compounds. Our synthesized compounds demonstrated significant antiproliferative activity when compared with the standards cisplatin and 5-fluorouracil, across a panel of six different tumor cell lines.

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids.

Considering early-stage drug discovery programs, the Ugi four-component reaction is a valuable, flexible, and pivotal tool, facilitating the creation of two new amide bonds in a one-pot fashion to effectively yield the desired α-aminoacylamides. Here, we highlight the reputation of this reaction approach to access number and scaffold diversity of a library of isatin-based α-acetamide carboxamide oxindole hybrids, promising anticancer agents, in a mild and fast sustainable reaction process. The library was tested against six human solid tumor cell lines, among them, non-small cell lung carcinoma, cervical adenocarcinoma, breast cancer and colon adenocarcinoma.

Palladium nanoparticles for the synthesis of phenanthridinones and benzo[]chromenes C-H activation reaction.

In the present work, derivatives of phenanthridine-6(5)-ones and benzo[]chromenes were efficiently prepared through an intramolecular C-H bond functionalization reaction catalyzed by photochemically synthesized Pd-PVP nanoparticles. The heterocycles were obtained intramolecular arylation of the corresponding -methyl--aryl-2-halobenzamide or aryl-(2-halo)benzyl ethers using KCO as base in a mixture of HO : DMA as solvent without additives or ligands. High yields of the heterocyclic compounds were achieved (up to 95%) using a moderately low catalyst loading (1-5 mol%) under an air atmosphere at 100 °C.

Ethanolic Extract from Fruits of , a Chilean Extremophile Plant. Assessment of Antioxidant Activity and In Vitro Cytotoxicity.

is a shrub with yellow flowers that reach up to two meters high, endemic of the Atacama Region in Chile. This species grows under special environmental conditions such as low altitude, arid areas, and directly sun-exposed habitats. In the present study, ethanolic extract was obtained from fruits of , and then partitioned in solvents of increasing polarity to obtain five fractions: hexane (HF), dichloromethane (DF), ethyl acetate (AF), and the residual water fraction (QF).

Antiproliferative and Antibacterial Activity of Polyporoid Fungi from Veracruz, Mexico.

Polyporoid fungi represent a vast source of bioactive compounds with potential pharmacological applications. The importance of polyporoid fungi in traditional Chinese medicine has led to an extensive use of some species of Ganoderma for promoting health and longevity because their consumption is associated with several bioactivities. Nevertheless, bioactivity of some other members of the Polyporaceae family has also been reported.

Coumarin-azasugar-benzyl conjugates as non-neurotoxic dual inhibitors of butyrylcholinesterase and cancer cell growth.

We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The compounds were evaluated as cholinesterase inhibitors, demonstrating a general preference, of up to 676-fold, for the inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Nine of the compounds behaved as stronger BuChE inhibitors than galantamine, one of the few drugs in clinical use against Alzheimer's disease.

Early pharmacological profiling of isatin derivatives as potent and selective cytotoxic agents.

Isatin derivatives have attracted a lot of interest for their potential in the development of new anticancer drugs. A library of 38 isatin derivatives, created through an Ugi four-component reaction, underwent an initial screening in a panel of six human solid tumor cell lines. The four most active derivatives were then selected for further testing.

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs.

A sequential strategy to access 10,11-dihydro-5-dibenzo[,][1,4]diazepinones (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald-Hartwig (B-H) or Chan-Lam (C-L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO) as CO surrogate (to avoid toxic CO handling) of readily available -phenylenediamines and either 1,2-dibromobenzene or 2-bromophenylboronic acid. The 10,11-dihydro-5-dibenzo[,][1,4]diazepinone could be synthezised in good yield using a sequential catalytic procedure, using both C-L and B-H approaches. Gratifingly, the use of the C-L reaction was more impressive, and afforded the dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst.

Microwave-induced one-pot synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole hybrids as antiproliferative agents and density functional theory study.

Herein, we outline a highly efficient PEG-4000-mediated one-pot three-component reaction for the synthesis of 3-imidazolyl indole clubbed 1,2,3-triazole derivatives (5a-r) at up to 96% yield as antiproliferative agents. This three-component protocol offers the advantages of an environmentally benign reaction, excellent yield, quick response time, and operational simplicity triggered by the copper catalyst under microwave irradiation. All the synthesized compounds were tested for antiproliferative activity against six human solid tumor cell lines, that is, A549 and SW1573 (nonsmall cell lung), HBL100 and T-47D (breast), HeLa (cervix), and WiDr (colon).

Additional Sarasinosides from the Marine Sponge Collected from the Bismarck Sea.

In our continuing efforts to describe the biological and chemical diversity of sponges from Kimbe Bay, Papua New Guinea, the known 30-norlanostane saponin sarasinoside C () was identified along with six new analogues named sarasinosides C, C, C, C, C, and C (-) from the sponge . The structures of the new compounds were elucidated by analysis of 1D and 2D NMR and HRMS data, as well as comparison with literature data. All new compounds are characterized by the same tetraose moiety, β-d-Xyl-(1→6)-β-d-GlcNAc-(1→2)-[β-d-GalNAc-(1→4)]-β-d-Xyl, as described previously for sarasinoside C, but differed in their aglycone moieties.

Antiproliferative effect of natural and semisynthetic polyethers from .

Squalene-derived polyethers are a unique class of compounds that display a great diversity of structures and a broad array of bioactivities, among which its notable antiproliferative activity stands out against various types of cancer cell lines. In this study, eighteen triterpene squalene-derived polyethers, including twelve natural products and six synthetic derivatives, obtained from the red alga Gil-Rodríguez & Haroun were screened for their antiproliferative activity against six cancer cell lines: A549, HBL-100, HeLa, SW1573, T-47D, and WiDr; and a structure-activity relationship (SAR) study was established.

Developed Bone Biomaterials Incorporated with MicroRNAs to Promote Bone Regeneration: A Systematic Review, Bioinformatics, and Meta-analysis Study.

This systematic review and meta-analysis focused on the effectiveness of biomaterials integrated with specific microRNAs (miRNAs) for bone fracture repair treatment. We conducted a comprehensive search of the PubMed, Web of Science, and Scopus databases, identifying 42 relevant papers up to March 2022. Hydrogel-based scaffolds were the most commonly used, incorporating miRNAs like miR-26a, miR-21, and miR-222, with miR-26a being the most prevalent.

Lipophilic modification of salirasib modulates the antiproliferative and antimigratory activity.

Salirasib, or farnesylthiosalicylic acid (FTS), is a salicylic acid derivative with demonstrated antineoplastic activity. While designed as a competitor of the substrate S-farnesyl cysteine on Ras, it is a potent competitive inhibitor of isoprenylcysteine carboxymethyl transferase. In this study, the antiproliferative activity on six different solid tumor cell lines was evaluated with a series of lipophilic thioether modified salirasib analogues, including those with or without a 1,2,3-triazole linker.

Laurequinone, a Lead Compound against .

Among neglected tropical diseases, leishmaniasis is one of the leading causes, not only of deaths but also of disability-adjusted life years. This disease, caused by protozoan parasites of the genus triggers different clinical manifestations, with cutaneous, mucocutaneous, and visceral forms. As existing treatments for this parasitosis are not sufficiently effective or safe for the patient, in this work, different sesquiterpenes isolated from the red alga have been studied for this purpose.

Conformationally Restricted Glycoconjugates Derived from Arylsulfonamides and Coumarins: New Families of Tumour-Associated Carbonic Anhydrase Inhibitors.

The involvement of carbonic anhydrases (CAs) in a myriad of biological events makes the development of new inhibitors of these metalloenzymes a hot topic in current Medicinal Chemistry. In particular, CA IX and XII are membrane-bound enzymes, responsible for tumour survival and chemoresistance. Herein, a bicyclic carbohydrate-based hydrophilic tail (imidazolidine-2-thione) has been appended to a CA-targeting pharmacophore (arylsulfonamide, coumarin) with the aim of studying the influence of the conformational restriction of the tail on the CA inhibition.

Identification and characterization of novel marine oxasqualenoid yucatecone against Naegleria fowleri.

Naegleria fowleri is an opportunistic protozoan, belonging to the free-living amoeba group, that can be found in warm water bodies. It is causative agent the primary amoebic meningoencephalitis, a fulminant disease with a rapid progression that affects the central nervous system. However, no 100% effective treatments are available and those that are currently used involve the appearance of severe side effects, therefore, there is an urgent need to find novel antiamoebic compounds with low toxicity.

Recirculating packed-bed biofilm photobioreactor combined with membrane ultrafiltration as advanced wastewater treatment.

Packed-bed biofilm photobioreactor combined with ultrafiltration membrane was investigated for intensifying the process for secondary wastewater effluent treatment. Cylindrical glass carriers were used as supporting material for the microalgal-bacterial biofilm, which developed from indigenous microbial consortium. Glass carriers allowed adequate growth of the biofilm with limited suspended biomass.