Design, synthesis, pharmacological evaluation, and in silico studies of the activity of novel spiro pyrrolo[3,4-d]pyrimidine derivatives.

In the present study, spiro compounds are shown to have distinctive characteristics because of their interesting conformations and their structural impacts on biological systems. A new family of functionalized spiro pyrrolo[3,4-d]pyrimidines is prepared via the one-pot condensation reaction of amino cyclohexane derivatives with benzaldehyde to prepare fused azaspiroundecanedione and azaspirodecenone/thione derivatives. A series of synthesized spiro compounds were scanned against DPPH and evaluated for their ability to inhibit COX-1 and COX-2. All compounds exhibit significant antiinflammatory activity, and they inhibited both COX-1 and COX-2 enzymes with a selectivity index higher than celecoxib as a reference drug. The most powerful and selective COX-2 inhibitor compounds were 11 and 6, with selectivity indices of 175 and 129.21 in comparison to 31.52 of the standard celecoxib. However, candidate 14 showed a very promising antiinflammatory activity with an IC50 of 6.00, while celecoxib had an IC50 of 14.50. Our findings are promising in the area of medicinal chemistry for further optimization of the newly designed and synthesized compounds regarding the discussed structure-activity relationship study (SAR), in order to obtain a superior antioxidant lead compound in the near future. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopic and elemental investigations.

CuO nanoparticles for green synthesis of significant anti-Helicobacter pylori compounds with in silico studies.

Helicobacter pylori (H. pylori) is a universal health intimidation as mentioned by the World Health Organization. The primary causal agent linked to a number of illnesses, including inflammation and the development of stomach ulcers, is Helicobacter pylori. Since, H. pylori develops antibiotic resistance quickly, current H. pylori treatment approaches are becoming less effective. Our research aims to highlight novel formulation antibiotics using CuO-NPs as catalysts and studied their activity as anti-helicobacter pylori supported by computational studies (POM analysis and molecular docking) software. They were designed for anti-Helicobacter Pylori action. All compounds revealed a bactericidal effect better than the reference McFarland standards.

Synthesis of novel pyrazolone candidates with studying some biological activities and in-silico studies.

Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory.

Synthesis, pharmacological evaluation, DFT calculation, and theoretical investigation of spirocyclohexane derivatives.

Polycyclic structures fused at a central carbon are of great interest due to their appealing conformational features and their structural implications in biological systems. Although progress in the development of synthetic methodologies toward such structures has been impressive, the stereo selective construction of such quaternary stereo centers remains a significant challenge in the total synthesis of natural products. From the computational calculations by Density Functional Theory along with the B3LYP as basis set, It is obvious that the all studied compounds are soft molecules and η varied from 0.069 for compound (10) to 0.087 for compound (15), while the compound (14) is treated as hard molecule, the value of η is 0.102, also the electronic transition within the soft compounds is easy as indicated from the △E, the compound (10) is absolute soft according to the (σ = 14.49 eV), while the compound (14) is treated as hard compounds (σ = 9.804 eV). The newly formed compounds exhibited both anti-inflammatory and antioxidant activities on HRBC homolytic and membrane stabilization and DPPH scavenging percent, respectively.

TiO2 nanoparticle as catalyst for an efficient green one-pot synthesis of 1H-3-Indolyl Derivatives as significant antiviral activity.

Titanium dioxide nanoparticles (TiO2- NPs) are produced in large quantities for an extensive range of applications. They retain variable physicochemical properties, which influence their bioactivity. The condensation synthesis of 3-acetylindol, thiophene-2-carbaldehyde and malononitrile in the existence of TiO2 nanoparticle yields 2-amino-6-(1H-indol-3-yl)-4-(thiophen-2-yl)-4H-pyran-3-carbonitrile derivatives. The yielded compound 2 reacted with (formic acid, formamide, ethyl chloroacetate, chloroacetyl chloride, thiourea and sodium nitrite). This three-combination system is safe, ecologically friendly, and non-toxic. The proposed system helped in time preservation and reduction in chemical consumption. The synthesized compounds were screened for antiviral activity against Vero cells (HAV). Antiviral impact percent for samples 2, 5, 6 and 7 versus HAV were 81.98, 91.05, 9.21, and 21.95%, respectively. The viral efficacy of Sample 5 was the strongest against HAV.

Design, Synthesis, Molecular Docking, and Evaluation Antioxidant and Antimicrobial Activities for Novel 3-Phenylimidazolidin-4-One and 2-Aminothiazol-4-One Derivatives.

On our way to discovering and developing compounds that have an antioxidant impact compared to ascorbic acid and other biological activities, we designed, synthesized, and evaluated a new series of heterocyclic moieties drugs (1-11) as antioxidants and antimicrobial agents. As starting moieties, these new candidates were derived from two promising heterocyclic compounds, imidazoldin-4-one and thiazol-4-one. Firstly, diphenylimidazol 1 was obtained because of the cyclo condensation one-pot ternary reaction of urea, aniline, and chloroacetic acid under thermal conditions. Out of this starting compound, we could design and create new vital rings such as purine and triazine as in compounds 5 and 6, respectively. Secondly, the start thiazole derivative 7 was obtained from the intermolecular cyclization of thiourea, chloroacetic acid, p-nitobezaldehyde in the presence of sodium acetate. We synthesized various derivatives from this second starting compound 7 by being subjected to different reagents such as aniline, phenylenediamine, phenylhydrazine, and barbituric acid to yield 8, 9, 10, and 11, respectively. Using ascorbic acid as the standard compound, the pharmacological testing for antioxidant activity assessment of the produced derivatives was evaluated against ABTS (2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). Candidate 6 exhibited the best activity as an antioxidant agent compared to ascorbic acid as a reference compound. Moreover, all compounds were evaluated as antimicrobial agents against a series of bacteria and fungi. Among all synthesized compounds, compound 6 achieved high efficiency against two types of fungi and four kinds of bacteria, as Clotrimazole and Ampicillin were used as the reference agents, respectively. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopical and elemental investigations.

Antiarrhythmic, serotonin antagonist and antianxiety activities of novel substituted thiophene derivatives synthesized from 2-amino-4,5,6,7-tetrahydro-N-phenylbenzo[b]thiophene-3-carboxamide.

A series of novel thiophene derivatives 3-17 were synthesized by initial reactions of 2-amino-4,5,6,7-tetrahydro-N-phenylbenzo[b]thiophene-3-carboxamide 1 and 2-amino-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carbonitrile 7 with different organic reagents. The structures of newly synthesized compounds were confirmed by IR, 1H NMR, MS spectral data and elemental analysis. Initially the acute toxicity of the compounds was assayed via the determination of their LD50. All the compounds were screened for their antiarrhythmic, serotonin antagonist and antianexiety activities and they showed high activity compared with procaine amide, lidocaine, diazepam and buspirone as positive controls. The detailed synthesis, spectroscopic data, LD50 and pharmacological activities of the synthesized compounds were reported.