This paper presents a Chemistry Team Game Tournament (TGT) as a didactic strategy to review stereochemistry concepts. For this purpose, a multilingual (English, Italian, French, and Portuguese) educational game, Stereochemistry Race, was developed on the online digital platform PlayingCards. The study involved the participation of 85 students from the following institutions: sixteen first-year Pharmacy students at the Federal University of Ceará (Brazil); twelve senior high school students at Colégio Maximus, in Fortaleza (Brazil); sixteen first-year Natural Sciences students and forty-one first-year Biotechnology students at the Università degli Studi di Genova (Italy). After the implementation of the tournament, the students evaluated the game, the match strategy, and their social and emotional interactions with their peers. To this end, data collection was carried out using a form that also included the UES-SF (User Engagement Scale-Short Form) engagement assessment model, which showed greater student participation and interest in stereochemistry studies than to traditional review classes.

Tumor-associated human carbonic anhydrases (hCAs), particularly isoforms hCA IX and hCA XII, are overexpressed in hypoxic regions of solid tumors and play a crucial role in regulating pH homeostasis, promoting cancer cell survival and enhancing invasiveness. These enzymes have emerged as promising therapeutic targets in cancer treatment, including photothermal therapy (PTT). PTT is a minimally invasive technique that uses light-absorbing agents to convert near-infrared (NIR) light into heat, effectively inducing localized hyperthermia and promoting cancer cell apoptosis. Recent advances in the design of hCA-targeted photothermal agents have shown promise in selectively targeting and ablating cancer cells while sparing healthy tissues. We explore here recent advancements in developing combination therapies that integrate hCA-targeted strategies with PTT for tumor treatment. By focusing on tumor-associated isoforms hCA IX and hCA XII, we underscore the potential of hCA inhibition to enhance both the efficacy and specificity of PTT in cancer therapy. We also address critical challenges and outline future directions, emphasizing the need to improve the biocompatibility, stability, and clinical translation of hCA-targeted photothermal agents. This mini review highlights the promise of combining hCA inhibition with PTT as an innovative therapeutic approach, aiming to advance more precise and effective cancer treatments.

Human carbonic anhydrases IX and XII (hCA IX/XII) are overexpressed in various solid tumors and play critical roles in tumor survival and progression, particularly under hypoxic conditions. In this study, a tail-focused design strategy was employed to synthesize thiazole-based chalcone derivatives bearing a sulfanilamide moiety as the zinc-binding group for selective inhibition of tumor-associated CA isoforms. Compound 5u emerged as the most potent, exhibiting strong inhibition of hCA IX/XII, outperforming acetazolamide and SLC-0111. In the NCI-60 panel, 5u showed broad-spectrum anticancer activity, with GI50 values below 2 μM in melanoma, breast, and colon cancer cell lines. Under hypoxic conditions, 5u demonstrated enhanced cytotoxicity in A375, A2058, SKMEL-2, and MDA-MB-231 cells. Molecular docking confirmed favorable binding to hCA IX/XII active sites. ADME predictions indicated good solubility and oral bioavailability, while DFT calculations supported its electronic stability. These results highlight 5u as a promising lead for dual hCA IX/XII-targeted cancer therapy.

INTRODUCTION:Benzoxaborole is a boron-based heterocyclic scaffold with remarkable potential in medicinal chemistry. Its unique chemical structure and compatibility with biological systems have enabled the development of innovative drug candidates. Benzoxaborole derivatives exhibit diverse biological activities, including antibacterial, antifungal, antiparasitic, antiviral, anticancer, and anti-inflammatory effects, making them valuable in addressing various medical challenges. AREAS COVERED:This manuscript reviews the medicinal chemistry literature and patent landscape from 2019 to 2024, focusing on the therapeutic potential of benzoxaborole-based compounds. EXPERT OPINION:Benzoxaboroles are gaining recognition as a versatile and innovative class of therapeutics with strong potential in infectious diseases, oncology, and inflammatory conditions. Their unique boron-containing scaffold enables diverse biological interactions and favorable pharmacokinetic properties. While clinical data are still emerging, early results and robust patent activity suggest significant therapeutic value. Advances in synthetic methods, targeted delivery, and computational design are accelerating their development. With continued focused research and strategic clinical validation, benzoxaboroles are well-positioned to address pressing medical challenges, particularly antimicrobial resistance, and could become an integral part of future treatment paradigms across multiple therapeutic areas.

This article examines the impact of a science competition (French Chemists' Tournament) on the engagement and performance of a graduate student team from the University of Montpellier as they compete against teams from some of the most prestigious French institutions. After outlining the French higher education system and the details of the tournament, we analyze the results of a questionnaire designed to assess participants' perceptions of their knowledge and skills, including communication, self-confidence, and motivation. Student interviews were also conducted.

Natural coumarins, a class of compounds found abundantly in various plants, are emerging as promising candidates in fight against cancer. Their ability to target multiple cancer-related processes has drawn significant interest from researchers. Natural coumarins exhibit anticancer effects through mechanisms such as inducing apoptosis, which is the programmed death of cancer cells, inhibiting cell proliferation, and disrupting angiogenesis, the process by which tumors develop their own blood supply to sustain growth. What makes coumarins particularly intriguing is their broad-spectrum activity against various types of cancer cells, from breast to lung to colon cancers. They interact with key molecular pathways that drive tumor progression, making them versatile agents in cancer therapy. Additionally, unlike many conventional chemotherapy drugs, natural coumarins generally have lower toxicity, which could translate to fewer side effects for patients. This characteristic makes them attractive as potential standalone treatments or as complementary therapies that enhance the efficacy of existing drugs while minimizing harm to normal cells. Ongoing research continues to explore the therapeutic potential of natural coumarins to better understand their full therapeutic potential and how they might work in combination with other anticancer agents. As the body of evidence grows, these natural compounds could become integral components of more effective and less harmful cancer treatment regimens, offering new hope for patients facing this challenging disease. This review was conducted by systematically analyzing the existing literature on natural coumarins and their anticancer potential.

Coladonin, a natural sesquiterpene coumarin ether isolated from Ferula tunetana, along with seven ester derivatives were investigated as inhibitors of human carbonic anhydrases IX and XII (hCA IX/XII). A series of coladonin-derived analogues (7a-g) was synthesized and tested against five CA isoforms (hCA I, II, IV, IX, XII). Coladonin 6 and its trifluoracetyl derivative 7e strongly and selectively inhibited hCA IX (K i = 90 and 70 nM, respectively) and hCA XII (K i = 210 and 110 nM, respectively). Compound 7e exhibited better selectivity on hCA IX than acetazolamide (AAZ). The antimelanoma and antiglioblastoma efficacy of coladonin 6 and 7e was evaluated in vitro under hypoxic conditions. Both compounds displayed significant antiproliferative effects, markedly better than those of the reference hCA IX/XII inhibitor SLC-0111 currently in clinical phase IIb. These results highlight coladonin 6 as a promising scaffold for developing selective hCA IX/XII inhibitors targeting hypoxic tumors.

This study describes the green synthesis and investigation of linear and nonlinear optical properties of three different porphyrins: 5,10,15,20-tetrakis(p-methoxyphenyl)porphyrin (H2MeTPP), 5,10,15,20-tetrakis(p- methoxyphenyl)porphyrinatocopper(II) (MeTPPCu), and 5,10,15,20-tetrakis(p-methoxyphenyl)porphyr- inatozinc(II) (MeTPPZn). Three thin films of these porphyrins each with a thickness of 465.3 nm were deposited on quartz wafers by thermal evaporation. Surface morphology and crystallite size of as-deposited thin films were analyzed using SEM and XRD, while molecular structures were confirmed through UV-Vis, IR, NMR, and HR-MS techniques. Optical properties were assessed using the Drude and Wemple-DiDomenico models. Their optoelectronic properties showed notable differences, with MeTPPZn showing the most promising electronic polarizability characteristics. It exhibited the highest dispersion energy (37.33 eV), indicating strong electron delocalization, and the smallest bandgap (1.24 eV), making it the most polarizable porphyrin. Moreover, it had the highest charge carrier concentration (1.54x1026 m- 3), refractive index (2.82), dielectric constants (e infinity = 7.37, eL = 7.94), plasma frequency (1.93x1015 Hz), and optical mobility (1.33x10-1 C.Sec.kg-1), coupled with the lowest optical resistivity (3.05x10-7kg & sdot;m3 & sdot;C-2 & sdot;s- 1), highlighting its exceptional potential for optoelectronic applications. Additionally, MeTPPZn showed the highest electric susceptibility, and molecular polarizability (1.90x10-- 22 cm3.mole-1), which facilitate the quicker separation of charge carriers and lower recombination losses. These attributes make MeTPPZn highly suitable for the fabrication of resistive-capacitive type thin-film sensors. Under varying illumination and humidity levels, the Ag/MeTPPZn/Ag bimodal sensor outperformed the Ag/H2MeTPP/Ag and Ag/MeTPPCu/Ag sensors, demonstrating that at up to 55 % RH, it is highly sensitive to resistance, while beyond 55 % RH, capacitance increases sharply and resistance remains saturated.

Boronic acids are an interesting but still poorly studied class of carbonic anhydrase inhibitors. Previous investigations proved that derivatives incorporating aromatic, arylalkyl, and arylalkenyl moieties are low micromolar to millimolar inhibitors for several α- and β-CAs involved in pathologic states. Here we report a high-resolution X-ray study on two classes of boronic acids (phenyl and vinyl) in complex with hCA II. Our results unambiguously clarify the binding mode of these molecules to the human carbonic anhydrase active site, which occurs through their tetrahedral anionic form, regardless of the nature of the organic scaffold. Data here presented contribute to the understanding of the inhibition mechanism of boronic acids that can be fruitfully used for the rational design of novel and effective isozyme-specific carbonic anhydrase inhibitors.

INTRODUCTION:Hypoxia is a key feature of solid tumors, associated with aggressive behaviors such as radiation and chemotherapy resistance, increased metastasis, and poor prognosis. Hypoxia-inducible factors (HIFs) are essential transcription factors that help tumor cells adapt to hypoxic environments by promoting the expression of pro-oncogenic genes. Reducing HIF activity presents a promising strategy for advancing cancer treatment. AREA COVERED:In this paper, the authors present an overview of recent studies on the development of HIF-1/2 inhibitors as potential anticancer drugs. The article offers a comprehensive analysis of the structural characteristics of these inhibitors and explores their relationship with anticancer activity, focusing on research conducted over the past decade, from 2015 to 2024. EXPERT OPINION:Because they play a big role in medicinal chemistry and the discovery of anticancer drugs, HIF inhibitors have always gotten a lot of attention and have been used to make a lot of important molecules with different biological effects, especially in the field of cancer research. Several techniques and chemical scaffolds have successfully targeted HIF-1α. However, additional research is required to sustain HIF-1α inhibition while maintaining anticancer activity. The FDA approval of Belzutifan provided researchers with an opportunity to conduct broader HIF-2 studies.

The benzoxaborinine scaffold, a homologue of benzoxaborole with an additional carbon atom in the boracycle, shows significant potential in developing new therapeutic agents. This study reports the synthesis, inhibition assays against four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, and anti-melanoma evaluation of 7-aryl(thio)ureido-substituted benzoxaborinines. Some derivatives, particularly compound 11, exhibited potent inhibitory activity (below 65 nM) against hCA IX and XII and stronger antiproliferative effects than SLC-0111 on human melanoma cells under hypoxia. Crystallographic studies of benzoxaborinine 3 adducts with hCA I and II demonstrated the binding mode of this chemotype, revealing that although both benzoxaborinine 3 and benzoxaborole 10 share a similar zinc-binding mode, the expanded ring in benzoxaborinine led to a different orientation within the active site. These findings suggest that benzoxaborinines hold promise for designing novel carbonic anhydrase inhibitors.

Over the last decades, the medicinal chemistry of boron-based compounds has been extensively explored, designing valuable small molecule drugs to tackle diseases and conditions, such as cancer, infections, inflammatory and neurological disorders. Notably, boron has proven to also be a valuable element for the development of inhibitors of the metalloenzymes carbonic anhydrases (CAs), a class of drug targets with significant potential in medicinal chemistry. Incorporating boron into carbonic anhydrase inhibitors (CAIs) can modulate the ligand ability to recognize the target and/or influence selectivity towards different CA isoforms, using the tail approach and boron-based tails. The electron-deficient nature of boron and its associated properties have also led to the discovery of novel zinc-binding CAIs, such as boronic acids and the benzoxaboroles, capable of inhibiting the CAs upon a Lewis acid-base mechanism of action. The present manuscript reviews the state-of-the-art of boron-based CAIs. As research in the applications of boron compounds in medicinal chemistry continues, it is anticipated that new boron-based CAIs will soon expand the current array of such compounds. However, further research is imperative to fully unlock the potential of boron-based CAIs and to advance them towards clinical applications.

Flavonoid derivatives are natural product analogues that have shown great interest for therapeutic applications as modulators of DNA methylation. In this article we report new synthesis pathways to access ten novel flavonoid derivatives (i.e. 3-halo-3-nitro-aza/thioflavanones) to be used as potential DNA methyltransferase inhibitors. These compounds have a micromolar inhibition against human DNA methyltransferase 3A in our in vitro fluorescence-based assay. Importantly, a docking study of representative compounds of this series in the enzyme pocket highlights a mode of interaction in the catalytic pocket of hDNMT3A that has never been described.

A series of thiochromenocarbazole imide (TCI) photosensitizers featuring carbonic anhydrase inhibitors (CAi) was designed to alleviate the consequences of PDT-induced hypoxia by merging the advantages of hCA IX knockdowns with PDT.

Metalloporphyrins are the natural light harvesting antennas and are extensively used as sensing and optoelectronic materials. Herein, we are reporting the synthesis and investigation of the optical properties of a novel octahedral metalloporphyrin, SnPMX. The structure of SnPMX is established by the IR, UV-visible, 1H NMR, and HRMS techniques. Thermal evaporation is used to grow thin films of SnPMX on quartz surfaces. The surface morphology and structural parameters of the as deposited thin films are investigated by the use of powder XRD and SEM. The linear and nonlinear optical parameters of the SnPMX are investigated by employing the WempleDiDomenico and Drude single oscillator models. The SnPMX presented a higher value of the lattice dielectric (epsilon L = 5.79) than the high frequency dielectric (epsilon infinity = 4.76) which confirmed the presence of free carriers and lattice vibrations. The short relaxation time (tau = 2.30 x 10-20 s), higher optical mobility (mu opt. = 9.19 x 10-9 C. Sec/Kg) and third order nonlinear susceptibility (chi 3 = 1.37 x 10-12 esu) support its potential use in optoelectronics and photonics. In the absorbing region, SnPMX presented 2.67 eV of direct optical band gap energy, and in the non-absorbing region, two distinct Urbach energies of 1.01 and 1.90 eV were observed, which indicate the electron-phonon or exciton-phonon interactions. These results indicate that SnPMX can be used for NLO and optical limiting applications.

IntroductionAntibacterial photodynamic therapy presents a promising alternative to antibiotics, with potential against multidrug-resistant bacteria, offering broad-spectrum action, reduced resistance risk, and improved tissue selectivity.Areas coveredThis manuscript reviews patent literature in the field of antibacterial photodynamic therapy through the period of 2019-2023. All data are from the US and European patent databases and SciFinder.Expert OpinionAntibacterial photodynamic therapy (PDT) is an appealing approach for treating bacterial infections, especially biofilm-related ones, by releasing reactive oxygen species (ROS) upon light activation. Its success is driven by a growing variety of photosensitizers (PSs) with tailored properties, like water solubility, controllable surface charge, and ROS generation efficiency. Among them, Aggregation Induced Emission (AIE)-type PSs are promising, demonstrating enhanced efficacy when aggregated in biological environments. However, the penetration of pristine PSs into bacterial biofilms within deep tissues or complex anatomical regions is limited, reducing their antibacterial effectiveness. To address this, nanotechnology has been integrated into antibacterial PDT to synthesize various nano-PSs. This adaptability allows seamless integration with other antimicrobial treatments, offering a comprehensive approach to combat localized infections, especially in dentistry and dermatology. By combining PSs with complementary therapies, antibacterial PDT offers a multifaceted strategy for effective microbial control and management.

INTRODUCTION:Photodynamic therapy (PDT) is a reactive oxygen species (ROS)-dependent treatment modality which has emerged as an alternative cancer therapy strategy. However, in solid tumors, the therapeutic efficacy of PDT is strongly reduced by hypoxia, a typical feature of many such tumors. The tumor-associated carbonic anhydrases IX (hCA IX) and XII (hCA XII), which are overexpressed under hypoxia are attractive, validated anticancer drug targets in solid tumors. Current challenges in therapeutic design of effective PDT systems aim to overcome the limitation of hypoxia by developing synergistic CA-targeted therapies combining photosensitizers and hCA IX/XII inhibitors. AREA COVERED:In this review, the current literature on the use of hCA IX/XII inhibitors (CAi) for targeting photosensitizing chemical systems useful for PDT against hypoxic solid tumors is summarized, along with recent progress, challenges, and future prospects. EXPERT OPINION:hCA IX/XII-focused photosensitizers have recently provided new generation of compounds of considerable potential. Proof of concept of in vivo efficacy studies suggested enhanced efficacy for CAi-PDT hybrid systems. Further research is needed to deepen our understanding of how hCA IX/hCA XII inhibition can enhance PDT and for obtaining more effective such derivatives.

Benzoxaborole is currently a scaffold of great relevance in medicinal chemistry. In 2016, it was reported to be a new and valuable chemotype for designing carbonic anhydrase (CA) inhibitors. Herein, using an in silico design, we report the synthesis and characterization of substituted 6-(1H-1,2,3-triazol-1-yl)benzoxaboroles. 6-Azidobenzoxaborole was described for the first time as a molecular platform to prepare libraries of inhibitors by a copper(I)-catalyzed azide-alkyne cycloaddition via a click chemistry strategy. With inhibition constants below 30 nM, some derivatives, such as compound 20, showed efficacy as selective hCA VII and IX inhibitors. The design hypothesis was validated by crystallographic investigation on the hCA II/20 adduct, which provided explanations over the different inhibition behavior observed against the five evaluated hCA isoforms. Overall, this study identified 20 as a new promising lead compound to develop novel anticancer agents targeting the tumor-associated hCA IX but also potent neuropathic pain relievers targeting hCA VII.

This report details the design of an online trilingual (English, French, and Portuguese) interactive virtual board game and its implementation at the Federal University of Ceara in Brazil. It was used as a fun alternative to assist chemistry and pharmacy undergraduate students in reviewing introductory concepts to organic reactions: enthalpy, entropy, Gibbs free energy, chemical equilibrium, chemical kinetics, nucleophiles, electrophiles, and reactive intermediates. Also, learners positively evaluated the game as an alternative method to conventional educational strategies for reviewing the content related to chemical reactivity.