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Calix[n]arenes, macrocycles constituted of 4-8 phenol moieties linked through methylene bridges, are stable molecules that can be selectively functionalised at the upper or lower rim. It has already been demonstrated that calixarene derivatives can be biologically or pharmacologically active compounds. More recently, suitably functionalised calixarenes and calixarene analogues (dihomooxacalixarenes, thiacalixarenes, calix[4]resorcinols, azacalixarenes, calixpyrroles, and pillarenes) were found to act as anticancer agents, at least in in vitro assays. We are reporting on the latest progress in this research field.

Reaction of L-cysteine with carbonyl compounds leads to thiazolidine derivatives which undergo a stereoselective conversion to two types of chiral bicyclic products bearing two or three stereogenic centers, including the first fused oxathiane-γ-lactam system.

In the review, current status of sulfoxides on the pharmaceutical market is discussed. In the first part of the article, natural sulfoxides will be described with a special focus on sulforaphane and amanitin, a mushroom toxin which has been developed as payload in antibody drug conjugates in the possible cancer treatment. Controversies associated with the medical use of dimethylsulfoxide are briefly described in the next section. In the part devoted to PPIs, the benefits of using pure enantiomers (chiral switch) are discussed. An interesting approach, repositioning of drugs is exemplified by new possible applications of modafinil and sulindac. The review is concluded by presentation of cenicriviroc and adezmapimod, both with the status of promising drug candidates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

2-Azabicycloalkanes: 2-azabicyclo[2.2.1]heptane and 2-azabicyclo[3.2.1]octane were used as a chiral platform for the construction of a set of 1,2,3-triazole, thiourea, and ebselen derivatives. Cytotoxicity and antiviral activity studies revealed the most promising potency for selected thioureas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Vulvovaginal candidiasis is primarily caused by Candida albicans ( C. albicans ). Here, a novel organoselenium compound (G20) was synthesized and evaluated for anti- Candida activity. Methods: Growth-inhibition studies and medium acidification assays to assess the inhibition of the yeast plasma membrane H + -ATPase (Pma1p) were carried out in vitro using G20. A self-nanoemulsifying formulation (SNEP) of G20 was prepared and evaluated for antimycotic activity in a mouse model. Results: G20 inhibited the growth of C. albicans through a mechanism that, at least in part, involves the inhibition of Pma1p. The G20-SNEP formulation significantly reduced vaginal colonization and vaginal inflammation relative to yeast-infected but untreated control mice. Conclusion: G20-SNEP exhibits potent antimycotic activity in a mouse model of vulvovaginal candidiasis.

Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration of mucosal and dermal tissues to life-threatening viral encephalitis. In most cases, standard treatment with acyclovir is sufficient to manage the disease progression. However, the emergence of ACV-resistant strains drives the need for new therapeutics and molecular targets. HSV-1 VP24 is a protease indispensable for the assembly of mature virions and, as such, constitutes an interesting target for the therapy. In this study, we present novel compounds, KI207M and EWDI/39/55BF, that block the activity of VP24 protease and consequently inhibit HSV-1 infection in vitro and in vivo. The inhibitors were shown to prevent the egress of viral capsids from the cell nucleus and suppress the cell-to-cell spread of the infection. They were also proven effective against ACV-resistant HSV-1 strains. Considering their low toxicity and high antiviral potency, the novel VP24 inhibitors could provide an alternative for treating ACV-resistant infections or a drug to be used in combined, highly effective therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The described inhibitors are covered by granted patents PL237651B1 and PL237652B1 and other related patent applications worldwide. The patents are owned by Wroclaw University of Science and Technology and Jagiellonian University., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Siderophores are unique ferric ion chelators produced and secreted by some organisms like bacteria, fungi and plants under iron deficiency conditions. These molecules possess immense affinity and specificity for Fe 3+ and other metal ions, which attracts great interest due to the numerous possibilities of application, including antibiotics delivery to resistant bacteria strains. Total synthesis of siderophores is a must since the compounds are present in natural sources at extremely small concentrations. These molecules are extremely diverse in terms of molecular structure and physical and chemical properties. This review is focused on achievements and developments in the total synthesis strategies of naturally occurring siderophores bearing arylthiazoline and aryloxazoline units., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Chiral sulfonamides with aromatic fragments are important chemical building blocks found widely in many natural products, catalysts, and molecules of biological importance. In this report, we describe the efficient synthesis of a series of chiral sulfonamides which, in addition to the aromatic part (phenyl, biphenyl, and dansyl units), possess N-heterocyclic systems. The described compounds were obtained by nucleophilic substitution of chiral N-heterocyclic amines and commercially available aromatic sulfonyl chlorides under mild conditions. All derivatives were examined in antiviral assay against AdV5, HSV-1, HPIV-3, HCMV, and EMCV viruses., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Masson SAS.)

Following recent experimental work demonstrating strong nonlinear optical properties, namely second harmonic generation of light, in crystals composed of 16,20-dinitro-(3,4,8,9)-dibenzo-2,7-dioxa-5,10-diaza[4.4.4]propellane molecules [A. Miniewicz, S. Bartkiewicz, E. Wojaczyńska, T. Galica, R. Zaleśny and R. Jakubas, J. Mater. Chem. C , 2019, 7 , 1255-1262] in this paper we aim to investigate "structure-property" relationships for a series of 16 propellanes presenting a wide palette of substituents with varying electron-accepting/donating capabilities. To that end, we use electronic- and vibrational-structure theories and a recently developed generalized few-state model combined with a range-separated CAM-B3LYP functional to analyze electronic and vibrational contributions to the first hyperpolarizability for the whole series of molecules. The variations in computed properties are large among the studied set of substituents and can reach an order of magnitude. It has been demonstrated that the maximum values of frequency-independent first hyperpolarizability are expected for strong electron-accepting NO 2 substituents, but only at the preferred position with respect to the electronegative oxygen atom in the 1,4-oxazine moiety. This holds for electronic as well as vibrational counterparts.

Organocatalysis is a very useful tool for the asymmetric synthesis of biologically or pharmacologically active compounds because it avoids the use of noxious metals, which are difficult to eliminate from the target products. Moreover, in many cases, the organocatalysed reactions can be performed in benign solvents and do not require anhydrous conditions. It is well-known that most of the above-mentioned reactions are promoted by a simple aminoacid, l-proline, or, to a lesser extent, by the more complex cinchona alkaloids. However, during the past three decades, other enantiopure natural compounds, the carbohydrates, have been employed as organocatalysts. In the present exhaustive review, the detailed preparation of all the sugar-based organocatalysts as well as their catalytic properties are described.

Carbon-carbon bond forming reactions, such as aldol reaction and condensation, belong to extremely desired transformations as manifested by >25,000 entries in SciFinder. Their stereoselective variant requires the use of an appropriate catalyst with a strictly defined structure. Hence, chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested in a stereoselective aldol reaction between cyclic/acyclic ketone and p -nitrobenzaldehyde both in organic and aqueous media. Among catalysts containing a chiral bicyclic backbone, amide based on 2-azabicyclo[3.2.1]octane and pyrrolidine units showed the best catalytic activity and afforded aldol product in excellent chemical yields (up to 95%) and good diastereo- and enantioselectivity ( dr 22:78, ee up to 63%).

N -Heterocycles are considered as desirable scaffolds for the development of novel lead compounds for anticancer drug research. Among them, phosphorus-containing amino-derivatives play a crucial role. A series of imines and products of their further reactions with P -nucleophiles were obtained starting from vicinal bisamines. Reaction of ethylenediamine and α-carbonyl esters yielded in novel unexpected products, which structures were confirmed by crystallographic measurements. The cytotoxic activity evaluation was done on a variety of cell lines including HUH7, AKH12, DAOY, UW228-2, D283, D425, and U251. Human umbilical vein endothelial cells (HUVECs) were used as control. Two of the tested compounds, bearing TADDOL-derived, and trifluoromethyl substituents showed a significant effect on cell viability, though comparable to nonmalignant cells.

A library of 21 novel chiral 1,2,3-triazole-based 2-azabicycloalkane conjugates was designed and synthesized using the copper(I)-catalyzed click reaction. The obtained hybrids were assessed for their antiproliferative potency against three selected human cancer cell lines: Hs294T (melanoma), MIA PaCa-2 (pancreas tumor) and NCI-H1581 (lung tumor). The majority of the synthesized compounds demonstrated moderate to potent activity, and some of them appeared more selective than cisplatin, with selectivity index exceeding 9.

In a search for new, selective antitumor agents, we prepared a series of sulfonamides built on bicyclic scaffolds of 2-azabicyclo(2.2.1)heptane and 2-azabicyclo(3.2.1)octane. To this end, aza -Diels-Alder cycloadducts were converted into amines bearing 2-azanorbornane or a bridged azepane skeleton; their treatment with sulfonyl chlorides containing biaryl moieties led to the title compounds. The study of antiproliferative activity of the new agents showed that some of them inhibited the growth of chosen cell lines with the IC 50 values comparable with cisplatin, and some derivatives were found considerably less toxic for nonmalignant cells.

One of the strategies employed by novel anticancer therapies is to put the process of apoptosis back on track by blocking the interaction between inhibitor of apoptosis proteins (IAPs) and caspases. The activity of caspases is modulated by the caspases themselves in a caspase/procaspase proteolytic cascade and by their interaction with IAPs. Caspases can be released from the inhibitory influence of IAPs by proapoptotic proteins such as secondary mitochondrial activator of caspases (Smac) that share an IAP binding motif (IBM). The main purpose of the present study was the design and synthesis of phosphorus-based peptidyl antagonists of IAPs that mimic the endogenous Smac protein, which blocks the interaction between IAPs and caspases. Based on the structure of the IAP antagonist and recently reported thiadiazole derivatives, we designed and evaluated the biochemical properties of a series of phosphonic peptides bearing the N-Me-Ala-Val/Chg-Pro-OH motif (Chg: cyclohexylglycine). The ability of the obtained compounds to interact with the binding groove of the X-linked inhibitor of apoptosis protein baculovirus inhibitor of apoptosis protein repeat (XIAP BIR3) domain was examined by a fluorescence polarization assay, while their potential to induce autoubiquitination followed by proteasomal degradation of cellular IAP1 was examined using the MDA-MB-231 breast cancer cell line. The highest potency against BIR3 was observed among peptides containing C-terminal phosphonic phenylalanine analogs, which displayed nanomolar K i values. Their antiproliferative potential as well as their proapoptotic action, manifested by an increase in caspase-3 activity, was examined using various cell lines.

Chiral sulfinyl compounds, sulfoxides, sulfoximines, sulfinamides, and other derivatives, play an important role in asymmetric synthesis as versatile auxiliaries, ligands, and catalysts. They are also recognized as pharmacophores found in already marketed and well-sold drugs (e.g., esomeprazole) and used in drug design. This review is devoted to the modern methods of preparation of sulfinyl derivatives in enantiopure or enantiomerically enriched form. Selected new approaches leading to racemic products for which the asymmetric variant can be developed in the future are mentioned as well.

In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1 H )-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1 R ,6 R )-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction.

A series of chiral sulfonamides containing the 2-azabicycloalkane scaffold were prepared from aza -Diels-Alder cycloadducts through their conversion to amines based on 2-azanorbornane or the bridged azepane skeleton, followed by the reaction with sulfonyl chlorides. The cytotoxic activity of the obtained bicyclic derivatives was evaluated using human hepatocellular carcinoma (HCC), medulloblastoma (MB), and glioblastoma (GBM) cell lines. Chosen compounds were shown to notably reduce cell viability as compared to nonmalignant cells.

New chiral bicyclic imines, enamines and amines were prepared via Horner-Wadsworth-Emmons reaction of hexahydroquinoxalin-2(1 H )-one-derived phosphonate, as the source of a phosphonate carbanion, and a wide range of structurally diverse carbonyl substrates. The simplicity of the synthetic protocol, high selectivity, and broad substrate scope are the main advantages of the presented methodology., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

For almost 20 years, thioureas have been experiencing a renaissance of interest with the emerged development of asymmetric organocatalysts. Due to their relatively high acidity and strong hydrogen bond donor capability, they differ significantly from ureas and offer, appropriately modified, great potential as organocatalysts, chelators, drug candidates, etc. The review focuses on the family of chiral thioureas, presenting an overview of the current state of knowledge on their synthesis and selected applications in stereoselective synthesis and drug development., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

New chiral tetrasubstituted aminophosphonic acid derivatives of hexahydroquinoxalin-2(1H)-one were synthesised via highly diastereoselective hydrophosphonylation of the corresponding imines with tris(trimethylsilyl) phosphite as phosphorus nucleophile. High asymmetric induction, good yields, mild reaction conditions, and ease of purification of the final products are the key advantages of the presented protocol.

The chemistry of cyclic imines has been gaining importance in the last decade because of their broad spectrum of applications and biological importance. This review focuses on the synthesis and utilization of these compounds with an emphasis on strategic transformations in organic chemistry. Electron-deficient sulfamate-derived and N-sulfonyl cyclic imines are also discussed as examples of versatile synthons in organic synthesis.

The review presents the achievements in the field of preparation of chiral 2-azanorbornyl derivatives and their application in various stereoselective reactions as well as in biomimetic studies.

Novel enantiopure policyclic nitrogen heterocycles have been obtained in the diastereoselective aza-Diels-Alder or Mannich reaction of dienes with imine formed in situ from ethyl glyoxylate and (1R,2R)-diaminocyclohexane.