Amidinoquinoxaline -oxides: synthesis and activity against anaerobic bacteria.

We present herein an in-depth study on the activity of amidinoquinoxaline -oxides 1 against Gram-positive and Gram-negative anaerobic bacteria. Based on 5-phenyl-2,3-dihydropyrimidoquinoxaline -oxide 1a, the selected structural variations included in our study comprise the substituents - to the -oxide function, the benzofused ring, substitution and quaternization of the amidine moiety, and the amidine ring size. Compounds 1 showed good to excellent antianaerobic activity, evaluated as the corresponding CIM and CIM values, and an antimicrobial spectrum similar to metronidazole.

Polyphosphoric Acid Esters Promoted Synthesis of Quinazolin-4(3)-imines from 2-Aminobenzonitrile.

A novel method for the synthesis of quinazolin-4(3)-imines (QIs) by trimethylsilyl polyphosphate (PPSE) promoted reaction of 2-aminobenzonitrile with secondary amides is reported. The reaction is general and allows for the synthesis of -aryl and -alkyl QIs with variable 2-substituents affording high yields. The procedure was extended to derivatives bearing additional functional groups.

Amidinoquinoxaline-Based Nitrones as Lipophilic Antioxidants.

The potential of nitrones (N-oxides) as therapeutic antioxidants is due to their ability to counteract oxidative stress, mainly attributed to their action as radical scavengers toward C- and O-centered radicals. Among them, nitrones from the amidinoquinoxaline series resulted in interesting derivatives, due to the ease with which it is possible to introduce proper substituents within their structure in order to modulate their lipophilicity. The goal is to obtain lipophilic antioxidants that are able to interact with cell membranes and, at the same time, enough hydrophilic to neutralize those radicals present in a water compartment.

Pro-Inflammatory Effects of NX-3 Toxin Are Comparable to Deoxynivalenol and not Modulated by the Co-Occurring Pro-Oxidant Aurofusarin.

The type A trichothecene NX-3, produced by certain strains, is similar to the mycotoxin deoxynivalenol (DON), with the exception that it lacks the carbonyl moiety at the C-8 position. NX-3 inhibits protein biosynthesis and induces cytotoxicity to a similar extent as DON, but so far, immunomodulatory effects have not been assessed. In the present study, we investigated the impact of NX-3 on the activity of the nuclear factor kappa B (NF-κB) signaling pathway in direct comparison to DON.

Synthesis of dihydroquinazolines from 2-aminobenzylamine: aryl derivatives with electron-withdrawing groups.

The sequential functionalization of 2-aminobenzylamine (2-ABA) followed by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with -aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SAr displacement, acylation and MW-assisted ring closure. Remarkably, the uncatalyzed arylation of 2-ABA led to the monosubstitution product using equimolar amounts of both reagents.

Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids.

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development.

Amidinoquinoxaline N-oxides: spin trapping of O- and C-centered radicals.

Amidinoquinoxaline N-oxides represent a novel family of heterocyclic spin traps. In this work, their ability to trap O- and C-centered radicals was tested using selected derivatives with different structural modifications. All the studied nitrones were able to trap radicals forming persistent spin adducts, also in the case of OH and OOH radicals which are of wide biological interest as examples of ROS.

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine.

A straightforward strategy for the synthesis of dihydroquinazolines is presented, which allows for the preparation of 3,4- and 1,4-dihydroquinazolines with different substitution patterns from 2-aminobenzylamine (2-ABA) as common precursor. The required functionalization of both amino groups present in 2-ABA was achieved by different routes involving selective acylation and cesium carbonate-mediated alkylation reactions, avoiding protection/deprotection steps. The heterocycles were efficiently synthesized in short reaction times by microwave-assisted ring closure of the corresponding aminoamides promoted by ethyl polyphosphate (PPE).