Sinteza i antimikrobno djelovanje novih derivata tienopirimidina

Reaction of heteroaromatic o-aminonitrile with ethyl N-/bis(methylthio)methyleneamino acetate resulted in annelation of a thieno/3,2-e/imidazo/1,2-c/pyrimidine moiety in a one step process. /1,2,4/Triazolo/4,3-c/thieno/3,2-e/pyrimidine derivatives were prepared by initial treatment of o-aminonitrile with carbon disulfide, followed by methylation with methyl iodide and subsequent reaction with benzhydrazide and thiosemicarbazide, respectively. Hydrazinothieno/2,3-d/pyrimidine was prepared by cyclization of heteroaromatic o-aminoester with formamide, followed by chlorination and subsequent displacement with hydrazine. Treatment of the hydrazine derivative with acetylacetone, benzaldehyde and acetic anhydride afforded pyrazolylpyrimidine, benzylidenehydrazonopyrimidine and trizolopyrimidine derivatives, respectively. Some of these derivatives exhibited pronounced antimicrobial activity.Reakcijom heteroaromatskih o-aminonitrila s etil N-/bis(metiltio)metilenamino acetatom u jednom sintetskom koraku došlo je do anelacije u tieno/3,2-e/imidazo/1,2-c/pirimidin. Derivati /1,2,4/triazolo/4,3-c/tieno/3,2-e/pirimidina pripravljeni su reakcijom o-aminonitrila s ugljikovim disulfidom, te metilacijom s metil-jodidom i naknadnom reakcijom s benzhidrazidom, odnosno tiosemikarbazidom. Hidrazinotieno/2,3-d/pirimidin je pripravljen ciklizacijom heteroaromatskog o-aminoestera s formamidom, te kloriranjem i supstitucijom s hidrazinom. Reakcijom hidrazinskog derivata s acetilacetonom, benzaldehidom ili anhidridom octane kiseline nastali su derivati pirazolilpirimidina, benzilidenehidrazonopirimidina, odnosno trizolopirimidina. Neki od tih derivata djeluju antimikrobno

Sinteza i antimikrobno djelovanje novih derivata tienopirimidina

Reaction of heteroaromatic o-aminonitrile with ethyl N-/bis(methylthio)methyleneamino acetate resulted in annelation of a thieno/3,2-e/imidazo/1,2-c/pyrimidine moiety in a one step process. /1,2,4/Triazolo/4,3-c/thieno/3,2-e/pyrimidine derivatives were prepared by initial treatment of o-aminonitrile with carbon disulfide, followed by methylation with methyl iodide and subsequent reaction with benzhydrazide and thiosemicarbazide, respectively. Hydrazinothieno/2,3-d/pyrimidine was prepared by cyclization of heteroaromatic o-aminoester with formamide, followed by chlorination and subsequent displacement with hydrazine. Treatment of the hydrazine derivative with acetylacetone, benzaldehyde and acetic anhydride afforded pyrazolylpyrimidine, benzylidenehydrazonopyrimidine and trizolopyrimidine derivatives, respectively. Some of these derivatives exhibited pronounced antimicrobial activity.Reakcijom heteroaromatskih o-aminonitrila s etil N-/bis(metiltio)metilenamino acetatom u jednom sintetskom koraku došlo je do anelacije u tieno/3,2-e/imidazo/1,2-c/pirimidin. Derivati /1,2,4/triazolo/4,3-c/tieno/3,2-e/pirimidina pripravljeni su reakcijom o-aminonitrila s ugljikovim disulfidom, te metilacijom s metil-jodidom i naknadnom reakcijom s benzhidrazidom, odnosno tiosemikarbazidom. Hidrazinotieno/2,3-d/pirimidin je pripravljen ciklizacijom heteroaromatskog o-aminoestera s formamidom, te kloriranjem i supstitucijom s hidrazinom. Reakcijom hidrazinskog derivata s acetilacetonom, benzaldehidom ili anhidridom octane kiseline nastali su derivati pirazolilpirimidina, benzilidenehidrazonopirimidina, odnosno trizolopirimidina. Neki od tih derivata djeluju antimikrobno

Synthesis, characterization, antibacterial activity of thiosemicarbazones derivatives and their computational approaches: Quantum calculation, molecular docking, molecular dynamic, ADMET, QSAR

The thiosemicarbazones and their derivatives have been recognized as antimicrobial agents against human pathogenic bacteria and fungi. Regarding these prospective, this study was designed to address the new antimicrobial agents from thiosemicarbazones and their derivatives. These derivatives were synthesized by multi-step synthesis methods, such as alkylation, acidification, esterification, and formed the 4-(4′-alkoxybenzoyloxy) thiosemicarbazones and its derivatives (THS1, THS2, THS3, THS4, and THS5). Afterward the synthesis, compounds were characterized by 1H NMR, FTIR spectra, and melting point. Later, the computational tools were applied to evaluate the drug likeness properties, bioavailability score, Lipinski rule, absorption, distribution, metabolism, excretion, and toxicity (ADMET). Secondly, the quantum calculations, for instance HOMO, LUMO and chemical descriptors, were calculated by the density functional theory (DFT). Finally, the molecular docking was performed against seven human pathogenic bacteria, black fungus (Rhizomucor mieh, Mucor lusitanicus, Mycolicibacterium smegmatis) and white fungus strains (Candida Auris, Aspergillus luchuensis, Candida albicans). To check and validate of molecular docking procedure and stability of docked complex for ligand and protein, the molecular dynamic was performed of docked complex. From the docking score with calculating the binding affinity, these derivatives could show a higher affinity than standard drug against all pathogens. From the computational details, it could be decided to do in-vitro test as antimicrobial activity against Staphylococcus aurious, Staphylococcus homonis, Salmonella typhi, and Shigella flexneria. The obtained result of antibacterial activity compared to standard drugs, and it was found that the synthesized compounds were almost same value of standard drug. Finally, it could be said from the in-vitro and in-silico study that the thiosemicarbazones derivatives are good antimicrobial agents

Supplements of an aqueous combination of Justicia adhatoda and Ocimum tenuiflorum boost antioxidative effects and impede hyperlipidemia

Background: Justicia adhatoda and Ocimum tenuiflorum, locally known as bashok and tulsi, are two ethnomedicinally important herbs that have been using as dietary supplements for several therapeutic applications. This study evaluated the combined effect of both the herbs as an antioxidative and antihyperlipidemic agent. Methods: Antihyperlipidemic effect was assessed in a high-fat diet-induced hyperlipidemic model in Wistar albino rats. The rats were treated orally with extracts of bashok (J adhatoda, 200 mg/kg bw), tulshi (O tenuiflorum, 200 mg/kg bw), and a combination of bashok and tulshi (50:50), as well as with a reference drug, atorvastatin (10 mg/kg/day), with or without high-fat diet for 14 days. The antioxidative effect was studied using established in vitro models. The studies were supported by experimentally testing the effects of the extracts on membrane stabilization and inhibition of protein denaturation. Results: The results showed that the serum lipid profile was significantly decreased in the different treatment groups, with bashok having the greatest effect. Body weights, total serum protein, LDH, and relative liver and adipose tissue weights were markedly restored towards baseline values, the lowest atherogenic index being achieved with the combined extract. The combination treatment significantly enhanced total phenolic content and antioxidative capacity and greatly potentiated membrane stabilization, but inhibition of protein denaturation was not significantly affected. Conclusion: The data demonstrate that a combination of Justicia adhatoda and Ocimum tenuiflorum could be developed as a food supplement with antioxidative and antihyperlipidemic benefits

Organic extracts of Asian plants potentially support thrombolysis in varied BMI groups

A number of plant-derived drugs have been prescribed for treating atherothrombotic disorders such as myocardial or cerebral infarction. Therefore, this study investigated the individual and combined antithrombotic effects of six Asian plants on individuals with various BMIs. Venous blood drawn from healthy volunteers was allowed to form clots and treated with six organic fractions of Ophiorrhiza harrisiana Heyne, Haldina cordifolia (Roxb.) Ridsdale, Eclipta alba (L.) Hassk, Syzygium operculatum L., Lantana camara L., and Acanthus ilicifolius Linn. using the clot-lysis method. The weight of the clot before and after treatment provided the percentage of clot lysis. Variations in clot lysis in different BMI groups were assessed. A. ilicifolius induced the most thrombolytic activity, whereas L. camara showed slightly lower thrombolytic activity. The maximum clot-lysis activity was primarily observed in different fractions of O. harrisana, H. cordifolia, E. alba, S. operculatum, and A. ilicifolius. However, chloroform fractions of all plants except O. harrisana and L. camara showed maximum activity in individual plants. O. harrisana, H. cordifolia, E. alba, S. operculatum, L. camara, and A. ilicifolius showed the highest significant (P < 0.5 and P < 0.001) clotlysis activity viz., 46.60±0.79% (ethyl acetate), 55.40±1.023% (chloroform), 48.86±1.35% (CCl4 ), 44.89±1.76% (chloroform), 29.17±1.12% (ethanol), and 56.318±1.64% (chloroform). Obtained results were verified by ligandreceptor interaction through in silico approach. In conclusion, H. cordifolia, E. alba, and A. ilicifolius demonstrated promising thrombolytic effects; therefore, it is recommended that they be studied further for their therapeutic potential