NUCLEOPHILIC SUBSTITUTION OF NITRO GROUP IN 1-METHYL- 5-NITRO-1,2,4-TRIAZOLE BY DIAMINOGLYOXIME

Изучен процесс взаимодействия 1-метил-5-нитро-1,2,4-триазола с многоцентровым бифункциональным О-нуклеофилом – диаминоглиоксимом. Показано, что исходный субстрат вступает в реакцию SNipso-замещения нитрогруппы с гидроксильными группами О-нуклеофила с образованием биологически активного соединения, объединяющего в единой молекуле фармакофорные фрагменты различного типа – 1,2,4-триазоловые гетероциклы и NH2-группы. Процесс сопровождается конкурентными реакциями образования триазолона и продукта его дальнейшего взаимодействия с исходным субстратом. С помощью веб-ресурса PASS Online осуществлен компьютерный скрининг, показано, что исходный субстрат и продукты реакции могут выступать потенциальными фармацевтическими субстанциями. The reaction between 1-methyl-5-nitro-1,2,4-triazome and a concerted bifunctional О-nucleophile – diaminoglyoxime was explored herein. The starting substrate was shown to engage into the SNipso-substitution of the nitro group by the О-nucleophile hydroxyls to furnish a bioactive compound whose single molecule combines different-type pharmacophoric moieties – 1,2,4-triazole heterocycles and NH2groups. The process came amid competitive reactions to form triazolone and a product from its subsequent reaction with the starting substrate. The PASS Online web-resource was used to perform computer-aided screening, demonstrating that the starting substrate and the reaction products can serve as potential pharmaceutical substances.

Synthesis of thiosulphonate and amino acid derivatives of benzochinone and predicted screening of their biological activity

Quinoid derivatives are attractive not only as interesting synthons for synthesis, but also as potential biologically active substances, so it is important to modify the compounds of the quinone series with different pharmacoform fragments. In this work, the structural design of chlorine and bromanyl disulfur-containing fragments, namely thiosulfonate, and chloranyl – a fragment of 4- aminobutanoic acid. Methods of synthesis were developed and physicochemical characteristics of thiosulfonate and amino acid derivatives were studied: 2,5-bis (thiosulfonate) -3,6-halogen -1,4- benzoquinones and 2,5-bis (3-carboxypropylamino) -3,6 - dichlorobenzoquinone. The prospects for the design of chlorine and bromanyl thiosulfonate fragments and chloranyl fragment of 4- aminobutanoic acid are confirmed by the results of predicting the biological activity of 5 a, b, 6 a, b, 7 using the online resource PASS Online. In particular, the substance 6a obtained by us is promising in terms of research on Antiviral (Picornavirus). The obtained results of predicted cytotoxicity screening indicate the feasibility of conducting experimental studies by in vitro methods on anticancer activity against cancer cell lines of hematopoietic and lymphoid tissue, lungs, skin, ovaries, blood, breast, kidney, colon, brain.

SYNTHESIS AND ANTIOXIDANT ACTIVITY OF (E)-3-(3-(4-OXO-4H-CHROMEN-3-YL)ACRYLOYL) 2H-CHROMEN-2-ONE DERIVATIVES

The aim is based on the results of the in silico prediction, to obtain and characterize a number of (E)-3-(3-(4-oxo-4H-chromen-3-yl)acryloyl)-2H-chromen-2-one derivatives, and also to study their antioxidant activity.Materials and methods. The synthesis of the target compounds was carried out by condensation of substituted 3-formylchromones and 3-acetylcoumarins under the acid catalysis conditions. 1H NMR spectra were recorded on the instruments of Bruker Avance-400 (400 MHz) and Bruker Avance-300 (300 MHz) in the solutions of CDCl3 or DMSO-d6. Mass spectra (ESI) were obtained on a Finnigan LCQ Advantage mass spectrometer (USA). The melting points of the compounds were determined on a PTP (M) instrument. Quantum-chemical calculations were carried out on the basis of a density functional theory using the Gaussian 09 program using the B3LYP/6-311G (d, p) method, as well as using the Way2Drug (PASS Online) online service. The antiradical activity of the compounds was studied by the DPPH test, and the chelating properties were assessed by the o-phenanthroline method.Results. 15 derivatives of (E)-3-(3-(4-oxo-4H-chromen-3-yl)acryloyl)-2H-chromen-2-one have been obtained and characterized. The calculations based on the density functional theory showed that the highest occupied molecular orbital exhibiting electron-donating properties is localized on the propenone fragment, which confirms the likelihood of the manifestation of antiradical properties. According to the prediction of the probable spectrum of the biological activity, the obtained compounds are more likely to exhibit their direct antioxidant activity. According to the results of the in vitro study of the antioxidant activity, it was found out that compounds 1-15 are the most active in relation to the DPPH radical, which confirms the obtained prognostic data.Conclusion. Thus, based on the in silico prediction data, 15 derivatives of (E)-3-(3-(4-oxo-4H-chromen-3-yl)acryloyl)-2H-chromen-2-one have been obtained and characterized, for which the method antioxidant activity has been studied in vitro. It was found out that compounds 1-15 exhibit the antiradical activity to a large extent.

Prediction of the biological activity of N-vinyl-3 (5)-methylpyrazole and polymers based on it

The results of studies on the prediction of the biological activity of N-vinyl-3(5)-methylpyrazole (VMP) using the PASS Online web resource and the CurveExpert program are presented. The possibility of evaluating the biological activity of VMP polymers is shown. It is established that the monomer and polymers based on VMP have their own biological activity.

Metabolitos secundarios, actividad biológica y etnobotánica de plantas de Santa Marta

Metabolitos secundarios, actividad biológica y etnobotánica de plantas de Santa Marta es una obra que reúne aspectos relacionados con la química de productos naturales vegetales de especies de la ciudad de Santa Marta (Magdalena). Se resaltan el tipo y la diversidad estructural de los metabolitos secundarios y la actividad biológica, producto del análisis de resultados reportados de los diferentes bioensayos. También se incluye la predicción de actividad biológica utilizando la herramienta PASS (predicción de espectros de actividad para sustancias biológicamente activa) de algunos de los metabolitos comunes. Se menciona igualmente el uso en medicina folclórica, a nivel mundial, de algunas especies de Santa Marta, relacionado en algunos casos con la actividad biológica reportada en la literatura científica. Las especies se presentan en el libro en orden alfabético por familia y se muestran resultados de ensayos biológicos de fracciones o extractos totales. Asimismo, se podrán encontrar esquemas y actividades de aprendizaje, además de una guía general para el uso del software PASS Online-Way2Drug, con la finalidad de motivar el desarrollo del aprendizaje autónomo o de competencias académicas.

Caracterização farmacognóstica, fitoquímica e avaliação in silico da atividade de monoterpenos isolados da espécie Dysphania ambrosioides (L.) Mosyakin & Clemants

O estudo tem por objetivo descrever os resultados obtidos dos parâmetros de qualidade farmacognóstico, prospecção fitoquímica e estudos in silico de monoterpenos isolados de Dysphania ambrosioides. Utilizou-se folhas e caules que foram secas e pulverizadas, os pós foram submetidos a testes farmacognóstico. Por meio de maceração com etanol obteve-se os extratos de caule (EEC) e de folhas (EEF), seguido de prospecção fitoquímica através de cromatografia em camada delgada. Para os estudos in silico selecionou-se os terpenos (1S,2S,3R,4S)-1-metil-4-(propan-2-il)-ciclohexano-1,2,3,4-tetrol (A); 1,2,3,4-tetrahidroxi-p-metano (B); (1R,2S)-3-pmeten-1,2-diol (C); (1R,4S)-p-met-2-en-1-ol (D); 1,4-dihidroxip-met-2-eno (E); 1-metil-4β-isopropil-1-ciclohexeno-4α, 5α, 6α-triol (F); Ascaridol (G), onde utilizou-se os programas Marvin JS, PreADMET, PASS online, Molinspiration Online, para avaliação dos aspectos físico-químicos, farmacocinéticos, toxicológicos e predição de atividade. Os pós foram classificados como grossos, com teor de umidade dentro dos parâmetros recomendados, sendo ausente as saponinas, pH neutro e baixa densidade. Na prospecção fitoquímica foram detectados triterpenos e esteroides, saponinas e heterosídeos flavônicos. Todos os compostos seguem a regra de Lipinski; foram bem absorvidos no trato gastrointestinal; C, D, E e G ligam-se fortemente às proteínas plasmáticas; C e D distribuíram amplamente no sistema nervoso central; D e E não foram metabolizadas pelo CYP e todas inibiram CYP; A e B não foram mutagênicas e F e G são carcinogênicas. As drogas vegetais apresentaram boa qualidade, sendo os terpenos presentes nestas amostras. Os estudos in silico apontam que as moléculas as moléculas C, F e G são promissoras para atividade anti-inflamatória, antineoplásica e antiprotozoária.

In Silico Anticancer activity and Caspase targeted study of Saponin rich fraction extracted from Caralluma fimbriata (Wall).

Caralluma fimbriata (Wall.) (Asclepiadaceae), is mentioned as vegetable in Indian Materia Medica and an affluent resource of saponins. It is reported in conventional medicine method of India as well as Arabia that C. fimbriata was extensively used for cancer treatment. Current study was planned to assess anticancer potential of saponin rich fraction from C. fimbriata using in silico and in vitro assays. Caratubersides A-G, a pregnane glycosides found in C. fimbriata were taken for in silico examination and processed through PASS Online software for the prediction of structure dependent pharmacological actions. Docking was carried out using Autodock Tool and Autodock Vina, revealed antineoplastic action of caratubersides along with apoptogenic potential. MTT assay was performed on MCF-7 cell line. Shell less chicken embryo culture assay was done for anti-angiogenic properties at different concentrations (1.5µg/ml, 3µg/ml, and 6µg/ml). Chromosomal aberrations assay was carried out in cultured human blood. And apoptogenic potential was estimated on MCF-7 cells using cleaved caspases 3 and caspase 8 cell based ELISA assay kit. Results of study showed that IC50 of saponin rich fraction of C. fimbriata was at 3μg/mL. Considerable (p <0.05) decreases were observed in angiogenic properties. Insignificant chromosomal aberrations were found in normal cells. Treatment of saponin rich part improved levels of caspases 3 as well as caspase 8 (ODs 1.35 and 1.68 respectively). From the study, saponin rich portion obtained from C. fimbriata displayed antiproliferative, anti-angiogenic actions along with apoptogenic prospective and no significant chromosomal aberrations were found in normal human cells.

Investigation of Excellent ACE Inhibitor Agents from Scurrula atropurpure and Dendrophthoe pentandra for Anti-Hypertension

The objective of this study was to investigate the bioactivity, toxicity, and interaction of the prepared bioactive compounds from Scurrula atropurpurea and Dendrophthoe pentandra with angiotensin-converting enzyme (ACE) macromolecule via an in-silico route. The bioactivity was investigated through Way2Drug PASS Online program. The drug-likeness property and human intestinal absorption of the bioactive compounds were evaluated through absorption, distribution, metabolism, and excretion (ADME) analysis. The interaction of bioactive compounds with ACE was examined via a molecular-specific docking analysis. The crystal structure of ACE was evaluated using the protein database 1086 chain A. The results elucidated that the prepared compounds exhibited potential bioactive agents for vasodilation, vasoprotective, and cardioprotective applications based on PASS analysis. The ADME analysis also revealed that the flavonol 3-O-D-glucoside did not violate any of the Lipinski's rule and had high gastrointestinal absorption. Furthermore, the results also suggested that the flavonol 3-O-D-glucoside of mistletoes had a harmless LD50 but was not recommended to be used for a long period. The molecular docking revealed that the flavonol 3-O-D-glucoside had the lowest binding energy with a value of −8.3 kcal.mol−1, suggesting the potential inhibitor for ACE. Generally, the toxicity and molecular docking analysis showed the compounds inhibited the ACE macromolecule with a series of flavonol > kaempferol > casticin > quercetin > quercitrin > isoquercitrin. Therefore, the S. atropurpurea and D. pentandra from Indonesian natural resources open new excellent potency for traditional herbal medicines, especially to treat hypertension. Keywords: ACE inhibitor, D. pentandra, hypertension, S. atropurpurea, traditional herbal

Computer-aided Identification of Synergetic Wound Healing Mechanisms Exhibited by Compounds in the Bio Synthesized Wound Dressing Material

A wound dressing material synthesized from the bio-composites of chicken fibrin, fish scale collagen impregnated with the spider web, and the ethanolic leaves extract of Mangifera indica (L.). The synthesized biomaterial was analyzed by GC-MS analysis. The present study involves identifying bioactive compounds that may heal wounds from the biosynthetic wound dressing material and the biological activities determined with the help of PASS software online prediction. PASS online software is used to explore the mechanism involved in healing wound compounds. Ten bioactive compounds identified as wound healing agents 2-methyl 4-Heptanol, 3-methoxy Hexane, Stigmasterol, Z-3,17-Octadecadien-1-ol acetate, 3-Chloro-5 Cholestene, 9,12,15 Octadecatrienoic acid 2,3 –Bis(acetyloxy) propyl ester(Z, Z, Z), Trans-Z-.alpha.-bisabolene epoxide, Beta carotene, Nopyl Acetate, 9,12 Octadecadienoic acid (Z, Z)phenylmethyl ester, and their bioactivities analyzed. Analyzed bio compounds found to exhibit wound healing mechanisms.