Ademir J. Camargo

A Structure-Activity Relationship (SAR) Study of Neolignan Compounds with Anti-schistosomiasis Activity

A set of eighteen neolignan derivative compounds with anti-schistosomiasis activity was studied by using the quantum mechanical semi-empirical method PM3 and other theoretical methods in order to calculate selected molecular properties (variables or descriptors) to be correlated to their biological activities. Exploratory data analysis (principal component analysis, PCA, and hierarchical cluster analysis, HCA), discriminant analysis (DA) and the Kth nearest neighbor (KNN) method were employed for obtaining possible relationships between the calculated descriptors and the biological activities studied and predicting the anti-schistosomiasis activity of new compounds from a test set. The molecular descriptors responsible for the separation between active and inactive compounds were: hydration energy (HE), molecular refractivity (MR) and charge on the C19 carbon atom (Q19). These descriptors give information on the kind of interaction that can occur between the compounds and their respective biological receptor. The prediction study was done with a new set of ten derivative compounds by using the PCA, HCA, DA and KNN methods and only five of them were predicted as active against schistosomiasis.

Synthesis, characterization, and computational study of a new dimethoxy-chalcone.

Chalcones are an important class of medicinal compounds and are known for taking part in various biological activities as in anti-inflammatory, anti-leishmania, antimitotic, and antiviral. Chemically, chalcones consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α,β-unsaturated carbonyl system. The wide action spectrum has attracted our attention to synthesize, crystallize, and characterize the dimethoxy-chalcone C18H18O3. Aiming to understand the process of crystal lattice stabilization, a combination of technique has been used including X-ray diffraction, infrared spectroscopy and computational molecular modeling. The theoretical calculations were carried out by the density functional method (DFT) with the M06-2X functional, with the 6-311+G(d,p) basis set. The vibrational wavenumbers were calculated and the scaled values were compared with experimental FT-IR spectrum. The intermolecular interactions were quantified and intercontacts in the crystal structure were analyzed using Hirshfeld surfaces. Bond distances and angles described by the X-ray diffraction and theoretical calculation are very similar. The C-H….O contacts contributing to assemble the supramolecular architecture are also responsible for the molecular structure assembly.

Biological and structure-activity evaluation of chalcone derivatives against bacteria and fungi

O presente trabalho descreve as atividades antibacterianas e antifungicas de diversas chalconas obtidas diretamente atraves da condensacao aldolica tipo Claisen-Schmidt das quais se determinou a concentracao inibitoria minima frente a diferentes microrganismos (bacterias Gram-positivas e Gram-negativas e fungos). Estruturas no estado solido cristalino de sete chalconas foram determinadas por analise de difracao de raios X (XRD). Estudos quimiometricos foram realizados com intuito de identificar uma potencial relacao entre estrutura e atividade.

Structure-Activity Relationship Study of Rutaecarpine Analogous Active Against Central Nervous System Cancer

Com o objetivo de relacionar os descritores geometricos e eletronicos dos derivados analogos da rutaercarpina com a atividade biologica contra o câncer do sistema nervoso central (CNS), calculos de quimica quântica molecular em nivel B3LYP/6-31(d) e analise estatistica foram realizados para os 21 derivados analogos da rutaecarpina. Dos 86 descritores moleculares calculados, 5 foram selecionados na construcao do modelo de analises de componentes principais (PCA). A componente PC1, a qual responde por 46,11% da variância total dos dados, foi capaz sozinha de discriminar completamente os compostos em duas classes: ativos e inativos. Todos os descritores moleculares selecionados pelo modelo PCA sao parâmetros eletronicos. A analise de agrupamento hierarquico (HCA) foi tambem aplicada aos descritores selecionados pelo modelo PCA. Baseado nos 5 descritores selecionados e possivel sugerir novos derivados ativos da rutaercarpina para serem sintetizados. Alem disso, um modelo de minimos quadrados parciais para analise discriminante (PLS-DA) supervisionado foi construido e aplicado com sucesso na discriminacao dos analogos a rutaercarpina, o qual foi validado usando um conjunto independente de compostos.

Molecular orbital calculations, experimental and theoretical UV spectra of granulatimides and didemnimides, biologically active polycyclic heteroaromatic alkaloids from the ascidian Didemnum granulatum

Abstract A detailed computational study was performed for compounds granulatimide, isogranulatimide, and didemnimides A, D, and E, using the semiempirical Austin model 1 quantum chemical method. The electronic features and structural parameters were confronted with the inhibition of the G2 cell cycle checkpoint of mammalian cancer cells. All compounds were submitted to a rigorous conformational analysis using the Tripos 5.2 force field implemented in the Spartan 5.01 program. The electronic density in specific regions of the molecules appears to play a pivotal role towards activity. The molecular planarity creates a broad negative electrostatic potential on the two sides of the active compounds (granulatimide and isogralulatimide) and a positive potential in their central core, while the non-planar compounds (didemnimides A, D, and E, which are inactive) present an asymmetric potential scattered over the molecules. These electrostatic potential features are likely to be the modulator of hydrophobicity or lipophilicity of the compounds, which appear correlated with activity. The hydrogen attached to the N atom of the pyrrole moiety of indole is more positive for active compounds than for the inactive molecules. The theoretical electronic spectra were obtained for all compounds using the configuration interaction method, with the AM1 routine. All transitions present π→π∗ nature. The theoretical results are in good agreement with experimental values.

Synthesis, Antimicrobial Activity and Structure-Activity Relationship of Some 5-Arylidene-thiazolidine-2,4-dione Derivatives

Derivatives of the thiazolidine-2,4-dione core represent a heterocyclic class with several correlated properties. In this context, the synthesis of structural analogues of these bioactive substances becomes attractive in the field of medicinal chemistry. These analogues act as antimicrobial agents against Gram-positives pathogens. The present work aimed to synthesize 10 different derivatives of 5-arylidene-thiazolidine-2,4-dione, employing urea as the catalyst in a solvent-free reaction medium, with yields that ranged from 45 to 99%. The compounds obtained were submitted to an antimicrobial assay against S. aureus ATCC 29213. Two compounds presented minimum inhibitory concentration of 62.5 and 32.5 μg mL and minimum bactericidal concentration < 500 μg mL, demonstrating their antibacterial potential. Principal component analysis was carried out to discriminate the compounds in active and inactive classes. Four geometric and electronic molecular descriptors were required to completely discriminate the compounds. The selected descriptors can guide us in designing new 5-arylidene-thiazolidine-2,4-dione derivatives with enhanced activity.

Um Estudo Químico Quântico e Quimiométrico da Styrylbenzylsulfones e seus Análogos com Atividade Citotóxica contra Células do Câncer de Próstata

O câncer e um termo generico para um grande grupo de doencas baseado no desenvolvimento rapido de celulas anormais que crescem alem dos seus limites usuais, e que podem se espalhar para outros orgaos. Este processo e referido como metastase. O câncer de prostata e o sexto tipo de câncer mais comum em todo o mundo, a quarta principal causa de morte por câncer no Brasil. As propriedades moleculares de 34 analogos de Styrylbenzylsulfones com atividade citotoxica contra celulas cancerosas humanas da prostata foi calculado atraves do metodo: Teoria do Funcional de Densidade com o nivel B3LYP/6-31G .Quatro descritores (ângulo diedral entre os atomos: 17, 18, 23 e 24; as ordens de ligacao entre atomos de 18-19 e 20-21; e polarizabilidade) foram responsaveis pela discriminacao do dois grupos de moleculas ( ativos e inativos) e para isto foi utilizado uma tecnica de reconhecimento de padrao: Analise do Componente Principal ( PCA ). Este modelo foi capaz de discriminar 20 ativos de 14 inativos dos analogos usando apenas uma componente principal, sendo responsavel por 51.20% da variância total e que permite melhor compreender a influencia desses descritores eletronicos na atividade citotoxica. DOI: 10.5935/1984-6835.20160037

Theoretical investigation on ruthenium tetraazaporphyrin as potential nitric oxide carrier in biological systems

Nitric oxide (NO) is an important chemical compound involved in many physiological and pathological processes in living organisms. However, nitric oxide is a very reactive radical that needs to be carried through organisms to reach the desired biological target. With the aim of developing new compounds that can be used as biomedical NO carrier agents we carried out a theoretical investigation at B3LYP/6-31 + G(d)/LANL2DZ level on the interaction of NO with RuTAP (Ruthenium tetraazaporphyrin) and Ru(L)TAP, where L = Clˉ, NH3, and Pyridine (Py)) and the oxidation state of Ru ranging from +1 to +3. The theoretical calculation results show that the geometric and electronic parameters of the Ru–NO bond are highly dependent on the oxidation state of Ru and of the chemical nature of ligand L at axial position. The results also show clearly that RuTAP and Ru(L)TAP are good potential candidates to be used as NO carriers in living organisms.