In this work we explore some theoretical and practical aspects of one-pot synthesis. The focal point of the study is the preparation of the thiazole heterocycle, with an emphasis on theoretical aspects of the organic and medicinal chemistry of this important privileged structure. The entire set of experimental procedures and characterization steps explored in this work has the potential to assist in the training and/or technical improvement of undergraduate students, and contribute to the teaching of chemistry in Brazilian higher education. It is worth emphasizing these aspects because the experiments shown in the proposed practices involve simple, rapid, low-risk, and low-cost procedures, making it perfectly feasible to reproduce them in undergraduate classes, even in laboratories with limited material resources. onepot one pot synthesis heterocycle structure andor or students education simple rapid lowrisk, lowrisk low risk, risk low-risk lowcost cost classes resources

Abstract Leveraging the antimicrobial potential of both naphthoquinones and semicarbazones, four semicarbazones (SMC1-SMC4) from lapachol with inherent antibacterial potential were designed. For the synthesis of the semicarbazones, a two-step synthetic route was proposed. Initially, lapachol was extracted from the Tabebuia genus tree and subsequently subjected to acid cyclization to yield α-lapachone (2), β-lapachone (3), β-lapachone-3-sulfonic acid (4), and 3-iodo-β-lapachone (5). To synthesize the semicarbazones (SMC1-SMC4), the naphthoquinones reacted with semicarbazide hydrochloride, resulting in products with yields ranging from 30% to 79%. Following this, the antibacterial efficacy of the compounds was evaluated against methicillin-resistant and non-resistant Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, and Klebsiella pneumoniae. Compounds 3, 4, and SMC4 demonstrated antimicrobial potential against resistant bacterial strains, and with MIC values of 0.03, 0.78 and 1.18 mM, respectively, against methicillin-resistant S. aureus. Naphthoquinone 3 demonstrated antimicrobial potential against susceptible S. aureus, E. coli, A. baumannii, and K. pneumoniae, and MIC values of 0.03, 0.52, 0.52 and 0.52 mM, respectively. Additionally, in silico assays suggested that compounds 3, 4 and SMC4 possess suitable ADMET pharmacokinetic profiles alongside low toxicity. SMC1SMC4 SMCSMC SMC1 SMC (SMC1-SMC4 designed twostep two step proposed Initially αlapachone α lapachone 2, 2 , (2) βlapachone β (3) βlapachone3sulfonic βlapachonesulfonic sulfonic (4) 3iodoβlapachone iodoβlapachone iodo 5. 5 . (5) SMC1SMC4, hydrochloride 30 79 79% this methicillinresistant methicillin nonresistant non aureus coli baumannii pneumoniae strains 003 0 03 0.03 078 78 0.7 118 1 18 1.1 mM respectively S E A K 052 52 0.5 Additionally toxicity SMC1SMC (SMC1-SMC (2 (3 (4 (5 7 00 0.0 07 0. 11 1. 05 (

Considering the chemical and pharmacological properties of semicarbazones, an interdisciplinary didactic sequence was developed to be applied in experimental classes of undergraduate courses in Pharmacy, Chemistry and related areas. This didactic sequence was planned in three steps, starting from the planning of the target molecule, a semicarbazone derived from helional, to its synthesis, physicochemical characterization (CCD, melting point, FTIR and UV-Vis) and in silico tests of its pharmacokinetic properties using the free software ADMETlab 2.0. The proposed target molecule has as molecular scaffold the 1,3-benzodiaxole nucleus and the semicarbazone function, aiming to obtain a molecule with promising anticonvulsant action and that can be obtained by a low cost and easy to execute methodology, which makes it attractive for use in experimental classes. Thus, the application of this didactic sequence aims to provide undergraduate students the opportunity to experience the process of drug development, applying techniques for planning, synthesis, characterization, and pharmacokinetic evaluation in silico. Besides reinforcing the interdisciplinary teaching of Medicinal Chemistry, applying in an integrated way the theoretical and practical knowledge of the disciplines of Organic Chemistry, Physical Chemistry, Pharmacology and Computational Chemistry. semicarbazones Pharmacy areas steps helional synthesis CCD, CCD (CCD point UVVis UV Vis UV-Vis 20 2 0 2.0 1,3benzodiaxole 13benzodiaxole benzodiaxole 1,3 1 3 function methodology Thus development 2. 3benzodiaxole 13 1,

Theranostic can be used to define therapeutic and imaging agents in a system. It is consisting of four components: signal emitter, therapeutic agent, targeting ligand and carrier. Naphthoimidazole and naphthoxazole are extended aromatic systems, and can participate in theranostic systems (TS) acting as a therapeutic agent and/or a signal emitter considering of their broad spectrum of biological activities and their optical properties of fluorescence emission. This systematic review investigated the applicability of the naphthoimidazole and naphthoxazole nuclei as constituents of TS and shows the synthesis methodologies described in the articles selected. Among the scientific articles suitable for the criteria of the systematic review, more than 35% described the evaluation of biological activities, mainly the naphthoimidazole derivatives, and approximately 18% explored the fluorescence emission of naphthoxazole derivatives and their applicability in biological systems. Among the selected articles 53% and 44% show synthetic routes for the preparation of naphthoxazoles and naphthoimidazoles, respectively. It was observed that both nuclei can be synthesized from various reagents, such as naphthoquinones, naphthols, naphthoic acids, aminonaphthoquinones and cyanophthalides. The results of this study suggests that naphthoimidazole and naphthoxazole derivatives are promising for application as components of TS, and there are various synthetic possibilities for obtaining these heterocycles.

RESUMEN Introducción: La membrana de cáscara de huevo (MCH) es un tejido que se encuentra entre la cáscara de huevo y la albúmina de los huevos que tiene propiedades atractivas para su uso en sistemas de administración de fármacos. Objetivo: Incorporar en MCH y utilizarla como fármaco modelo en estudios de liberación. El cambio de color y el análisis FTIR del biopolímero demostraron la incorporación de nimesulida en MCH. Resultados: La captación del fármaco fue de 176,83 y 122,69 mg g-1 por MCH natural y reticulado. Los estudios de liberación se llevaron a cabo utilizando un sistema de flujo espectrofotométrico en líquido intestinal simulado pH 7,4. Los perfiles de liberación mostraron que después de 60 minutos el 54,55 y el 42,58 % del fármaco se liberó de la MCH natural y reticulada, respectivamente. Los parámetros cinéticos indicaron que la liberación del fármaco se describió mejor mediante el modelo de Higuchi y mediante una liberación no Fickian. Conclusión: De acuerdo con estos resultados, el MCH tiene el potencial de convertirse en una matriz polimérica para sistemas de liberación de fármacos.

SUMMARY Introduction: Eggshell membrane (ESM) is a tissue found between the eggshell and the albumen of eggs that has attractive properties for use in drug delivery systems. Aim: To incorporate in ESM and used it as a model drug in release studies. The color change and FTIR analysis of the biopolymer proved the incorporation of nimesulide in ESM. Results: The drug uptake was 176.83 and 122.69 mg g-1 by natural and cross-linked ESM. Release studies were carried out using a spectrophotometric flow system in simulated intestinal fluid pH 7.4. The release profiles showed that after 60 minutes 54.55 and 42.58 % of the drug were released from natural and cross-linked ESM, respectively. Kinetics parameters indicated that drug release was better described by the Higuchi model and through a non-Fickian release. Conclusion: Considering these results is proved that ESM has the potential to become a polymeric matrix for drug release systems.

RESUMO Introdução: a membrana da casca do ovo (MCO) é um tecido encontrado entre a casca e o albúmen de ovos que possui propriedades atrativas para uso em sistemas de liberação de fármacos. Objetivo: incorporar à MCO e utilizá-la como fármaco modelo em estudos de liberação. Mudança de coloração e análises de FTIR do biopolímero comprovaram a incorporação da nimesulida na MCO. A incorporação do fármaco foi de 176,83 e 122,69 mg g-1 na MCO natural e reticulada, respectivamente. Resultados: os estudos de liberação foram realizados usando um sistema de fluxo espectrofotométrico em fluido intestinal simulado pH 7,4. Os perfis de liberação mostraram que após 60 minutos 54,55 e 42,58 % do medicamento foram liberados da MCO natural e reticulada, respectivamente. Os parâmetros cinéticos indicaram que a liberação do fármaco foi mais bem descrita pelo modelo de Higuchi e por meio de uma liberação não Fickiana. Conclusão: considerando estes resultados, fica comprovado que a MCO tem potencial para se tornar uma matriz polimérica para sistemas de liberação de fármacos.

RESUMEN Introducción: Investigaciones recientes han informado del potencial citotóxico de las hidrazonas contra varias líneas de células cancerosas. Objetivo: Evaluar la actividad anticancerígena in vitro y el perfil farmacocinético de seis compuestos hidrazónicos sintetizados, identificados como vainillina 1-ftalazinilhidrazona (VAN-1); vainillina 2,4-dinitrofenilhidrazona (VAN-2); fenilhidrazona cinamal-dehído (CIN-1); cinamaldehído de isonicotinoil hidrazona (CIN-2); cinamalde-hído 1-ftalazinilhidrazona (CIN-3); y 2,4-dinitrofenilhidrazona cinamaldehído (CIN-4). Se evaluó la actividad citotóxica frente a cuatro líneas celulares cancerosas. Metodología: Los parámetros farmacocinéticos de absorción, distribución, metabolismo, excreción y toxicidad (ADME/T) de las hidrazonas se evaluaron mediante el programa PreADMET. Resultados: Las hidrazonas derivadas del cinamaldehído (CIN-1 y CIN-2) mostraron una alta actividad citotóxica contra las líneas celulares leucémicas (HL-60) y glioblastomas (SF-295). El perfil farmacocinético de las hidrazonas mostró que, en general, las hidrazonas mostraban características satisfactorias de ADME/T. Además, se observó que CIN-2 presentó el perfil in silico más prometedor, presentando alta absorción intestinal, perfil de distribución deseable relacionado con la unión a proteínas plasmáticas, excreción renal adecuada y baja toxicidad. El perfil ADME/T del compuesto CIN-1 destacó su potencial como agente antineoplásico prometedor con acción sobre el SNC, más específicamente contra los glioblastomas.

SUMMARY Introduction: Recent research has reported the cytotoxic potential of hydrazones against various strains of cancer cells. Aim: To evaluate the anticancer activity in vitro and the pharmacokinetic profile of six synthesized hydrazonic compounds, identified as vanillin 1-phthalazinylhydrazone (VAN-1); 2,4-dinitrophenylhydra-zone vanillin (VAN-2); phenylhydrazone cinnamaldehyde (CIN-1); isonicotinoyl hydrazone cinnamaldehyde (CIN-2); cinnamaldehyde 1-phthalazinylhydrazone (CIN-3); and 2,4-dinitrophenylhydrazone cinnamaldehyde (CIN-4). The cytotoxic activity was evaluated against four strains of cancer cells. Methodology: The pharmacokinetic parameters of absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of the hydrazones were evaluated using the PreADMET program. Results: Hydrazones derived from cinnamaldehyde (CIN-1 and CIN-2) showed high cytotoxic activity against leukemic (HL-60) and glioblastomas (SF-295) cell lines. The pharmacokinetic profile of the hydrazones showed that, in general, the hydrazones presented satisfactory characteristics of ADME/T. In addition, it was observed that CIN-2 presented the most promising in silico profile, showing high intestinal absorption, desirable distribution profile related to plasma protein binding, adequate renal excretion, and low toxicity. The ADME/T profile of the CIN-1 compound highlighted its potential as a promising antineoplastic agent with action of the CNS, more specifically against glioblastomas.

RESUMO Introdução: Pesquisas recentes relataram o potencial citotóxico das hidrazonas contra várias linhagens de células cancerígenas. Objetivo: Validara atividade anti-câncer in vitro e o perfil farmacocinético de seis compostos hidrazônicos sintetizados, identificados como vanilina 1-ftalazinil-hidrazona (VAN-1); vanilina 2,4-dinitrofenil-hidrazona (VAN-2); cinnamaldeído de fenil-hidrazona (CIN-1); cinamaldeído isonicotinoil-hidrazona (CIN-2); 1-ftalazinil-hidrazona de cinnamaldeído (CIN-3); e cinamaldeído de 2,4-dinitrofenil-hidrazona (CIN-4). A atividade citotóxica foi avaliada contra quatro linhagens de células cancerígenas. Metodologia: Os parâmetros farmacocinéticos de absorção, distribuição, metabolismo, excreção e toxicidade (ADME/T) das hidrazonas foram avaliados utilizando o programa PreADMET. Resulados: As hidrazonas derivadas do cinnamaldeído (CIN-1 e CIN-2) apresentaram alta atividade citotóxica contra as linhagens celulares leucêmicas (HL-60) e de glioblastomas (SF-295). O perfil farmacocinético das hidrazonas mostrou que, em geral, as hidrazonas apresentaram características satisfatórias de ADME/T. Além disso, observou-se que a CIN-2 apresentou o perfil in silico mais promissor, exibindo alta absorção intestinal, perfil de distribuição desejável relacionado à ligação às proteínas plasmáticas, excreção renal adequada e baixa toxicidade. O perfil ADME/T do composto CIN-1 destacou seu potencial como um agente antineoplásico promissor com ação do SNC, mais especificamente contra glioblastomas.

Multicomponent reactions are attractive for the development of bioactive substances, being a one-pot synthesis allows a quick and efficient synthesis, and allows the construction of a diversity of privileged structures. The Debus-Radziszewski reaction, a classic example of a multicomponent reaction for obtaining 2,4,5-tri-substituted imidazole, was used to compose a didactic sequence to be applied in undergraduate courses in the following disciplines: Organic Chemistry, Experimental Chemistry, Pharmaceutical Chemistry and Medicinal Chemistry. Thus, the classes were planned and applied, one theoretical and two experimental, the synthesis of lofin (2,4,5-triphenyl-1H-imidazole) and the characterization of the product. The Debus-Radziszewski reaction for the preparation the lofin, proved to be suitable for practical class of multicomponent reactions, as it uses accessible reagents and equipment, it is easy to do and the students can follow the progress of the reaction visually. In addition, the didactic sequence inserts students in a contextualized and interdisciplinary way in the practical chemistry procedures, employing a classic reaction, but with current perspectives of Organic and Medicinal Chemistry, such as the synthesis of the privileged fragments of bioactive compounds.

Several scientific works demonstrate the chemical and medicinal importance of hydrazone compounds. In this regard, the present paper proposes some practical classes of chemoinformatics and organic chemistry, using investigative and illustrative strategies, to teach the synthesis of a hydrazone and a N-acylhydrazone with proven biological activity. The motivating element used for the development of this didactic material was the use of commercial drugs, such as hydralazine and isoniazid, as alternative reagents for the synthesis of the target compounds. The sequence of experimental classes was planned to demonstrate the role of chemistry in the development of new drugs, to estimulate the curiosity of undergraduate students and to facilitate learning and the assimilation of the contents.

Leishmaniasis is endemic anthropozoonosis considered to be a severe public health problem. The treatment with pentavalent antimonials presents high toxicity motivating the search for effective and less toxic drugs. Hydrazones and N-acylhydrazones are functional groups that are prominent in Medicinal Chemistry, including as antiprotozoals. In this context, five hydrazones derived from the natural aldehydes were synthesized and the molecular structures were suitably determined to employ uni and bidimensional 1H and 13C NMR techniques. The antileishmanial activity of all hydrazones was determined against promastigote forms of Leishmania amazonensis, and the compounds HDZ-3, HDZ-4, and HDZ-5 showed the best results, with IC50 of 9.00, 38.10 and 26.30 µM, respectively. In the cytotoxic evaluation against RAW macrophages, HDZ-4 presented the least cytotoxic (CC50 = 222.24 µM) and the higher selectivity. Lipinski’s descriptors of the hydrazones were calculated, and the compounds HDZ-3 and HDZ-5 were more promising. These hydrazones are hybrids of natural aldehydes with drugs, the first is the result of the junction of the cinnamaldehyde with isoniazid, and the second of the vanillin with hydralazine. The results highlighted the Markush isonicotinoylhydrazone and phthalazinylhydrazone groups, molecular structures that are present in HDZ-3 and HDZ-5 and are therefore considered innovators in the development of antileishmanial drugs.

Resumo O presente estudo refere-se ao impacto do uso de agrotóxicos sobre a saúde humana no Submédio do Vale do São Francisco. Por meio de entrevistas objetivou-se analisar a influência dos condicionantes sociais, culturais e econômicos no processo saúde-doença dos trabalhadores expostos a agrotóxicos. Para a coleta de dados foram entrevistados 339 trabalhadores rurais de perímetros irrigados dos municípios de Juazeiro-BA e Petrolina-PE. Todos do sexo masculino, sendo 182 (53,7%) proprietários rurais e 157 (46,3%) empregados, predominando indivíduos entre 40 e 59 anos entre os proprietários e abaixo de 39 anos entre os trabalhadores. Mais de 50% apresentou baixo nível de escolaridade e 55,2% tinha rendimentos mensais menor ou igual a 2 salários mínimos. Muitos sabem da importância do uso de EPIs e da obrigatoriedade do receituário agronômico para a utilização e a compra de agrotóxicos, entretanto cerca de 40% não usam EPIs ou fazem uso de forma incompleta e 28,9% não apresentam receituário durante a compra. Mais de 9% dos participantes relataram casos de intoxicação, no entanto, menos de 7% procuraram atendimento especializado. Os trabalhadores sabem que o uso de agrotóxicos nas lavouras os expõem a situações de risco, mas essa informação não é suficiente para alterar a conduta no exercício laboral.

Abstract This study refers to the impact of the use of pesticides on human health in the São Francisco River Valley region, in which, through semi-structured interviews, the objective was to analyze the influence of social, cultural and economic determinants on the health-disease process of workers exposed to agrochemicals. For data collection, 339 rural workers from irrigated perimeters of the cities of Juazeiro, in the State of Bahia, and Petrolina, in the State of Pernambuco, were interviewed. All were male, of which 182 (53,7%) were rural owners and 157 (46,3%) were employees, predominantly between 40 and 59 years of age among owners and under 39 among workers. Over 50% have a low level of schooling and 55.2% of them have monthly incomes less than or equal to 2 minimum wages. Many of them know about the importance of wearing personal protective equipment (PPE) and the mandatory license for the use and purchase of agrochemicals. However, about 40% do not use PPE or use it inadequately and 28.9% do not have a license to purchase. More than 9% of participants reported cases of intoxication, however, less than 7% sought specialized care. Workers are aware of the risks that the use of agrochemicals expose them to risk situations, but this does not encourage them to change their worksite behavior.

Resumo O presente estudo refere-se ao impacto do uso de agrotóxicos sobre a saúde humana no Submédio do Vale do São Francisco. Por meio de entrevistas objetivou-se analisar a influência dos condicionantes sociais, culturais e econômicos no processo saúde-doença dos trabalhadores expostos a agrotóxicos. Para a coleta de dados foram entrevistados 339 trabalhadores rurais de perímetros irrigados dos municípios de Juazeiro-BA e Petrolina-PE. Todos do sexo masculino, sendo 182 (53,7%) proprietários rurais e 157 (46,3%) empregados, predominando indivíduos entre 40 e 59 anos entre os proprietários e abaixo de 39 anos entre os trabalhadores. Mais de 50% apresentou baixo nível de escolaridade e 55,2% tinha rendimentos mensais menor ou igual a 2 salários mínimos. Muitos sabem da importância do uso de EPIs e da obrigatoriedade do receituário agronômico para a utilização e a compra de agrotóxicos, entretanto cerca de 40% não usam EPIs ou fazem uso de forma incompleta e 28,9% não apresentam receituário durante a compra. Mais de 9% dos participantes relataram casos de intoxicação, no entanto, menos de 7% procuraram atendimento especializado. Os trabalhadores sabem que o uso de agrotóxicos nas lavouras os expõem a situações de risco, mas essa informação não é suficiente para alterar a conduta no exercício laboral.

Abstract This study refers to the impact of the use of pesticides on human health in the São Francisco River Valley region, in which, through semi-structured interviews, the objective was to analyze the influence of social, cultural and economic determinants on the health-disease process of workers exposed to agrochemicals. For data collection, 339 rural workers from irrigated perimeters of the cities of Juazeiro, in the State of Bahia, and Petrolina, in the State of Pernambuco, were interviewed. All were male, of which 182 (53,7%) were rural owners and 157 (46,3%) were employees, predominantly between 40 and 59 years of age among owners and under 39 among workers. Over 50% have a low level of schooling and 55.2% of them have monthly incomes less than or equal to 2 minimum wages. Many of them know about the importance of wearing personal protective equipment (PPE) and the mandatory license for the use and purchase of agrochemicals. However, about 40% do not use PPE or use it inadequately and 28.9% do not have a license to purchase. More than 9% of participants reported cases of intoxication, however, less than 7% sought specialized care. Workers are aware of the risks that the use of agrochemicals expose them to risk situations, but this does not encourage them to change their worksite behavior.

Skin cancer is a frequent neoplasm in Brazil and this, is observed the importance of the development of new sunscreens using simple methodologies capable of reducing production costs. In this context, six symmetric acyclic azines were synthesized and characterized, with reaction yields between 54 and 84%, short reaction times (5 to 10 min), and manual grinding as an energy source. Sunscreens 10 %(m/m) of these compounds were produced for the in vitro determination of the solar protection factor UVB (SPF-UVB), of the the six formulations containing the synthesized azines, four showed higher photoprotective capacity in the UVB region (AZN-BZD, AZN-2OH, AZN-4OH and AZN-CIN), with SPF-UVB equivalent or higher than benzophenone-3 (BZF) and at the octylmethoxycinnamate (OMC), commercial chemical filters. The AZN-VAN and AZN-4DAB formulations presented high photoprotective capacity in the UVA region, resulting in lower SPF-UVB when compared to the other synthesized azines, but were still superior to the BZF and equivalent to the OMC. All the azines synthesized showed superior FPS-UVB to their precursor aldehydes, evidencing the increase of the photoprotective capacity due to the insertion of the azine group.

In Brazil, the development of new chemical entities (NEQ) is still limited to small advances in the academic and public research sectors, the authors understand that this is a sector of the pharmaceutical industry that needs encouragement. Accepting that education transforms society, educate students in the development of bioactive molecules, it’s a way to stimulate the national pharmaceutical industry to invest in the sector. Thus, this work brings a didactic sequence, applicable in undergraduate courses, which exemplifies some stages of development of the NEQ through its rational planning. The synthesis of a 1,3,4-oxadiazole heterocycle was planned and its potentiality assessed through the Lipinski’s Rule of Five (RO5), using the ChemSpider® database. Once in accordance with RO5, the heterocycle was prepared using a simple and accessible methodology, using microwaves for domestic use as heating source. The 2-phenyl-5-(pyridin-4-yl)-1,3,4-oxadiazole was synthesized by oxidative cyclization of acylhydrazone and an overall yield of 90%. So was possible to demonstrate in a practical way some steps for the development of a substance with potential biological activity and thus to attract greater interest of undergraduate students by this follow-up of the Medicinal Chemistry.

<p>Medicinal Chemistry is a multidisciplinary discipline and the discovery of new bioactive molecules is one of its objectives. Molecular Hybridization (MH) is a strategy of rational design of new prototypes, where the lead compound is produced through an adequate fusion of pharmacophoric sub-unities. Undergraduate laboratory experiments for Medicinal Chemistry education with a focus on MH are scarce. Therefore, the present paper describes a practice class for some undergraduate courses (Pharmacy, Chemistry and/or Chemical Engineering) involving drug development and MH that can be performed at low cost. In this work, alternative materials such as paracetamol and sulfadiazine tablets were used to engage student's attention and to contextualize important concepts of MH. The experiment describes the synthesis of a new compound involving the azo coupling between an aromatic amine (sulfadiazine) and a phenol (paracetamol) to show undergraduate students a practical example of MH. In this case, SciFinder^® - a search website of the American Chemical Society - was also demonstrated and utilized as a search tool in the proposed experimental class.</p>

This paper reports the use of alternative materials for teaching experimental chemistry. In this context, nimesulide and propranolol tablets were used to teach chemical concepts about acid-base reactions according to Brönsted-Lowry protonic Theory. Important topics of Organic, Analytical and Pharmaceutical Chemistry were discussed, such as purification by acid-base extraction, solubility of organic compounds in aqueous solutions, buffers, the dissociation constant (pKa), potentiometric titration and ionization of drugs in biological fluids. The purification of propranolol and nimesulide from tablets produced yields of 75% and 90%, respectively. The experimental values of pKa for both drugs were in agreement with those from the literature.