IR and UV-VIS spectroscopic analysis of a new compound: N-[1-(4-hydroxyphenyl) aminoethilyden]-4-[1-(3,5,5,8,8-pentamethyl-6,7-dihydronaphtalen-2-yl)-ethenyl] phenylcarbohydrazide

INTRODUCTION: Hydrazones are compounds that can be considered as hydrogenated azo compounds or as derivatives of hydrazine (H2N-NH2) in the structure of which one hydrogen atom at each nitrogen is replaced by a hydrocarbon group. In this work, we discuss the possibilities for analysis of a newly synthesized hydrazone of the retinoid bexarotene with acetaminophen using infrared (IR) and ultraviolet-visible (UV-VIS) spectroscopy.  AIM: The purpose of this study is to perform Fourier-transfrom infrared (FTIR) and UV-VIS spectroscopic analysis of a newly synthesized hydrazone of bexarotene. MATERIALS AND METHODS: А newly synthesized hydrazone derivative was obtained according to the basic scheme of synthesis of bexarotene analogs. Infrared spectra 500-4000 cm-1 were taken on a Bruker FTIR spectrometer using ATR—a plug with a Smart iTR adapter. Spectra in the range 190–325 nm were recorded using UV-VIS spectrophotometer T60 UV with UVWin Software 6.0. RESULTS: After a detailed comparison of the data obtained in the IR analysis of the reagents and the newly obtained hydrazone, a similar position and intensity of the spectral bands are reported. However, there are displacements in spectral bands and significant differences corresponding to the structural changes that have occurred. Different values for the wavelength of maximum absorption were measured with a UV-VIS spectrophotometer for bexarotene, Paracetamol, and the newly synthesized compound. CONCLUSION: In order to confirm the data obtained by FTIR and UV-VIS spectroscopy, a further reversed-phase high-performance liquid chromatography-ultraviolet (HPLC-UV) analysis of the new hydrazone derivative should be performed

FT-IR spectral analysis for a newly obtained structure analog of bexarotene

INTRODUCTION: Retinoids are natural and synthetic compounds part of the family of polyisoprenoid lipids. These compounds are involved in several important physiological processes in the human body because of their ability to bind to different nuclear receptors. Retinoids are used in the therapy of some precancerous lesions, the treatment of acute promyelocytic leukemia (APL), T-cell lymphoma, and the prevention of malignancies in high-risk cancer groups. In this work we discuss the possibilities for analysis of the newly synthesized hydrazone of the retinoid bexarotene.  AIM: The purpose of this study is to conduct FTIR spectral analysis of newly synthesized hydrazone of bexarotene.MATERIALS AND METHODS: Infrared spectra 500-4000 cm-1 were taken on a Bruker FTIR spectrometer using ATR - a plug with Smart iTR adapter.RESULTS: The infrared spectra of the newly synthesized compound were strikingly similar in the relative positions and intensities of the resulting peaks, confirming its close structural relationship with bexarotene. Despite the structural similarity, there were significant differences that point to the introduction of a substituent and the formation of a new hydrazone derivative.CONCLUSION:  In order to confirm the data obtained by FTIR spectroscopy, a further reversed-phase HPLC-UV analysis of the new hydrazone derivative should be performed

The Role Of Artificial Intelligence In Drug Design

Artificial intelligence (AI) aims to simulate human thought and actions. It is an effective tool for various functions, including problem-solving and data classification.In recent years, AI has found numerous applications in the pharmaceutical sector. It is utilized in drug design, optimization of the manufacturing process, adherence to correct drug intake, prediction of treatment outcomes, processing of biomedical and clinical data, analysis of gene expression patterns, and detection of pandemic outbreaks. In modern drug design, AI plays a crucial role in creating molecular libraries, identifying new drug candidates with optimal properties, and predicting the biological functions of drugs with a protein structure.This article aims to present opportunities for optimizing the drug design process through the use of AI.To achieve this goal, a literature review method was used. Articles reviewed were selected from PubMed, Scopus, and Google Scholar databases.AI enables a more systematic search model and allows for the estimation of its parameters. The application of AI in drug design provides opportunities for process optimization, reducing the use of toxic reagents in synthesis. Additionally, AI can address key challenges in traditional drug design methods, such as low success rates, limited target options, poor transition from preclinical to clinical trials, lengthy processes, and high costs

Antibacterial activity of 4-isopropyl-phenyl-methylidene-4- [1- (3,5,5,8,8-pentamethyl-6,7-dihydronaphthal-2-yl) ethenyl] benzohydrazyde

The increase in antibiotic resistance of microorganisms encourages the constant search for new compounds. Studies on the activity of hydrazones identify them as promising compounds for further microbiological research. The aim of the present study is to determine the antibacterial activity of newly synthesized 4-isopropyl-phenyl-methylidene-4- [1- (3,5,5,8,8-pentamethyl-6,7-dihydronaphthalen-2-yl) ethe- nyl] benzohydrazide, an analog of the antineoplastic preparation bexarotene. The assay was performed against clinical isolates of Escherichia coli and Staphylococcus aureus

Synthesis and Characterization of Bexarotene Derivatives with Potential Biological Activity // Получаване и охарактеризиране на бексаротенови производни с потенциална биологична активност

The dissertation deals with the preparation and characterization of the newly synthesized derivatives of the synthetic retinoid bexarotene. The continued and intensive study of the role of retinoids in the complex of differentiation, cell proliferation, and cellular growth processes determines the major potential for the using of retinoids (natural and synthetic) in the treatment of a number of abnormalities arising from abnormal cell development. Of particular interest is the possibility of their use in the treatment of neoplastic processes in the body. Bexarotene is a third-generation retinoid and is used in the treatment of T-cell skin cancer. In addition to its proven application in oncology, there are a number of data on the effects of neurological and autoimmune processes in the body. For the preparation of bexarotene derivatives, a three-step synthetic scheme has been developed. Involving the preparation of hydrazide and the subsequent interplay with carbonyl compounds to form the target hydrazones. Hydrazide-hydrazone compounds have attention in the last few decades because of the diverse pharmacological effects they possess. Hydrazones and their derivatives are known to exhibit a wide range of pharmacological effects such as antioxidant, anti-inflammatory, analgesic, antimicrobial, anthelmintic, anti-tuberculosis, etc. The development of the hydrazone class of compounds has made significant progress and many new aspects of application have been discovered. The resulting hydrazide hydrazones have been characterized structurally by instrumental methods including the use of infrared spectroscopy, 1H-NMR spectroscopy, and mass spectrometry. A validated HPLC method for the determination of bexarotene and its derivatives alone and in mixtures has been successfully applied. The antioxidant potential of the newly obtained bexarotene derivatives was evaluated using three different approaches - electron transfer capability - ABTS test, hydrogen atom transfer-DPPH test, as well as an electrochemical pathway. With the help of theoretical approaches, the possibilities for metabolic activation of bexarotene have been successfully identified, also its metabolites and new derivatives evaluated. The mechanisms by which the metabolites of the newly prepared compounds can potentiate liver damage through specific interactions with biological macromolecules (DNA and proteins) in the liver have been identified and summarized. The possibility of producing dermal metabolites has also been determined. // [BG] Дисертационния труд разглежда получаването и охарактеризирането на новосинтезирани производни на синтетичния ретиноид бексаротен. Продължаващото и интензивно изучаване на ролята на ретиноидите в комплекса от процеси на диференциация, пролиферация на клетки и регулация на клетъчния растеж обуславя големия потенциал за приложение на ретиноиди (естествени и синтетични) при лечението на редица нарушения, произтичащи от анормалното клетъчно развитие. Като с особен интерес се разглежда възможността за употребата им в терапията на неопластични процеси в организма. Бексаротенът се отнася към ретиноидите от трето поколение и намира приложение в терапията на Т-клетъчен кожен карцином. Освен утвърденото си приложение в онкологията редица са данните за ефекти при неврологични и автоимунни процеси в организма. За получаване на производни на бексаротен е разработена триетапна синтетична схема, включваща получаване на хидразид и последващо взаимодействие с карбонилни съединения до формиране на целевите хидразони. Хидразид-хидразоновите съединения привличат вниманието през последните няколко десетилетия поради разнообразните фармакологични ефекти, които притежават. Известно е, че хидразоните и техните производни проявяват широк спектър от фармакологични ефекти като антиоксидантен, противовъзпалителен, аналгетичен, антимикробнен, антихелминтен, противотуберкулозен и т.н. Развитието на хидразоновия клас съединения бележи значителен прогрес и се разкриват множество нови аспекти на приложение. Получените хидразид-хидразони са охарактеризирани структурно посредством инструментални методи включително прилагане на инфрачервена спектроскопия, 1Н-ЯМР-спектроскопия и масспектрометрия. Успешно е приложен и валидиран HPLC метод за определяне на бексаротен и негови производни самостоятелно и в смеси. Проведена е оценка на антиоксидантния потенциал на новополучените бексаротенови производни посредством три различни подхода – способност за електронен пренос – ABTS-тест, пренос на водороден атом-DPPH-тест, както и по електрохимичен път. С помощта на теоретични подходи успешно са идентифицирани възможностите за метаболитно активиране на бексаротен, оценени са неговите метаболити и новополучени производни. Идентифицирани и обобщени са механизмите, посредством които метаболитите на новополучените съединения могат да потенциират чернодробно увреждане, чрез специфични реакции на взаимодействие с биологичните макромолекули (ДНК и протеини) в черния дроб. Също така е определена и възможността за получаване на дермални метаболити.[BG] Дисертационния труд разглежда получаването и охарактеризирането на новосинтезирани производни на синтетичния ретиноид бексаротен. Продължаващото и интензивно изучаване на ролята на ретиноидите в комплекса от процеси на диференциация, пролиферация на клетки и регулация на клетъчния растеж обуславя големия потенциал за приложение на ретиноиди (естествени и синтетични) при лечението на редица нарушения, произтичащи от анормалното клетъчно развитие. Като с особен интерес се разглежда възможността за употребата им в терапията на неопластични процеси в организма. Бексаротенът се отнася към ретиноидите от трето поколение и намира приложение в терапията на Т-клетъчен кожен карцином. Освен утвърденото си приложение в онкологията редица са данните за ефекти при неврологични и автоимунни процеси в организма. За получаване на производни на бексаротен е разработена триетапна синтетична схема, включваща получаване на хидразид и последващо взаимодействие с карбонилни съединения до формиране на целевите хидразони. Хидразид-хидразоновите съединения привличат вниманието през последните няколко десетилетия поради разнообразните фармакологични ефекти, които притежават. Известно е, че хидразоните и техните производни проявяват широк спектър от фармакологични ефекти като антиоксидантен, противовъзпалителен, аналгетичен, антимикробнен, антихелминтен, противотуберкулозен и т.н. Развитието на хидразоновия клас съединения бележи значителен прогрес и се разкриват множество нови аспекти на приложение. Получените хидразид-хидразони са охарактеризирани структурно посредством инструментални методи включително прилагане на инфрачервена спектроскопия, 1Н-ЯМР-спектроскопия и масспектрометрия. Успешно е приложен и валидиран HPLC метод за определяне на бексаротен и негови производни самостоятелно и в смеси. Проведена е оценка на антиоксидантния потенциал на новополучените бексаротенови производни посредством три различни подхода – способност за електронен пренос – ABTS-тест, пренос на водороден атом-DPPH-тест, както и по електрохимичен път. С помощта на теоретични подходи успешно са идентифицирани възможностите за метаболитно активиране на бексаротен, оценени са неговите метаболити и новополучени производни. Идентифицирани и обобщени са механизмите, посредством които метаболитите на новополучените съединения могат да потенциират чернодробно увреждане, чрез специфични реакции на взаимодействие с биологичните макромолекули (ДНК и протеини) в черния дроб. Също така е определена и възможността за получаване на дермални метаболити

QSAR modeling for prediction of binding to DNA or proteins of dermal metabolites of newly synthesized hydrazones

IntroductionOver the last decade, there has been a significant increase in the scientific knowledge about cancer, which has accordingly led to the development and increase of interest in new medicines and therapeutic approaches with potential applications in oncology. Activity research and the identification of potential therapeutic and toxic effects of bexarotene-like structures underpin the development of new approaches to the treatment of a number of untreated diseases.This requires a further and in-depth study of the potential of newly synthesized compounds to produce active metabolites.AimIn view of the potential for dermal administration of bexarotene, the potential for toxic metabolism in the skin needs to be investigated.Materials and MethodsFor the purpose the OECD (Q) SAR Application Toolbox was used. It is a software application for evaluating the properties of chemicals based on their molecular structure.ResultsThe application of the model for predicting metabolic changes makes it possible to assess the risk based on the chemical structure of the compounds.ConclusionThe skin metabolic prediction of new hydrazones of third-generation retinoid bexarotene indicates that not one of them predicts binding to DNA or proteins

In Silico Evaluation of Terpene Interactions with Inflammatory Enzymes: A Blind Docking Study Targeting Arachidonic Acid Metabolism

Terpenes represent a structurally diverse class of natural compounds with increasing scientific interest due to their potential anti-inflammatory properties. This study investigates the in silico binding behavior of six plant-derived terpenes—α-pinene, β-pinene, menthol, camphor, limonene, and linalool—against four key enzymes in the arachidonic acid (AA) metabolic pathway: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and phospholipase A2 (PLA2). AA serves as a reference for binding energy comparison. Blind rigid-body molecular docking is performed using AutoDock 4.2 and the Lamarckian Genetic Algorithm, with 100 runs per ligand–enzyme pair and the energy-based selection of optimal poses. The analysis includes binding energy (ΔG), inhibition constants (Ki), root-mean-square deviation (RMSD), and residue-level interactions. Several terpenes exhibit favorable binding energies and inhibition constants across the evaluated enzymes. For COX-1 and COX-2, menthol and camphor show low Ki values, indicating stable binding. Menthol and limonene also show the strongest affinities for PLA2, exceeding AA. The focus is on compounds with potential to modulate arachidonic acid metabolism. In this context, β-pinene engages the catalytic site of PLA2, linalool forms multiple contacts within key regions of 5-LOX, and menthol, α-pinene, and β-pinene align with functionally important regions in both COX isoforms. These targeted interactions suggest that the highlighted compounds may selectively interfere with enzymatic activity in inflammation-related pathways. By modulating key steps in AA metabolism, these terpenes may influence the biosynthesis of pro-inflammatory mediators, offering a promising avenue for the development of safer, plant-derived anti-inflammatory agents. The findings lay the groundwork for further experimental validation and the structure-based optimization of terpene-derived modulators

COMPARISON OF ANTIMICROBIAL EFFICACY OF THREE TYPES OF MOUTHWASH, CONTAINING CHLORHEXIDINE-CHLORBUTANOL, ALCOHOL-ESSENTIAL OILS AND PROPOLIS-MENTHA OIL COMBINATIONS

Mouthwash is an antiseptic solution intended to reduce the microbial load in the oral cavity, although other mouthwash might be given for other reasons such as for their analgesic, anti-inflammatory or anti-fungal action. A study was carried out to compare the antibacterial and antifungal properties of three mouthrinse preparations - both containing commercial used antiseptic combinations (chlorhexidine 0,100% + chlorbutanol 0,500% and alcohol 21,60% + essential oils) and one with natural active ingredients (propolis 2,00% + mentha oil 0, 042%). The antibacterial and antifungal activity of three types of mouthwash were tested on three microbial strains - Staphylococcus aureus, Escherichia coli and Candida albicans by two alternatives of agar diffusion tests – “cup plate” technique and disc-diffusion test. The results showed the highest antimicrobial activity of the chlorhexidine-chlorbutanol combination. Mouthwash containing propolis with mint oil demonstrated activity only against S. aureus strain. It turned out that testing the antimicrobial activity of mouthwash with alcohol with essential oils with the agar diffusion method is not representative. For 24 hours with this mouthwash, no inhibition zones were observed in none of the strains at any concentration. Our assumption is that alcoholic solutions are exuding and bacteria starts to grow.</jats:p