Synthesis of New Pyrazole Derivatives,Their Anti-Inflammatory and Analgesic Activities,and Molecular Docking Studies

Russian Journal of General Chemistry - A new series of coupled benzofuran derivatives that contain the trifluoromethyl group and pyrazole moiety is synthesized for evaluation of their...     

Synthesis,Anticancer, Antioxidant,Anti-Inflammatory,Antimicrobial Activities,Molecular Docking,and DFT Studies of Sultams Derived from Saccharin

A series of N-substituted saccharins namely 2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetonitrile (2) and (alkyl 1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetate (3a–g) were synthesized, in moderate to excellent yields, from commercially available starting materials by two different approaches and their chemical structures were characterized by spectroscopic techniques (¹H-NMR, ¹³C-NMR, IR, and MS). All the synthesized compounds were evaluated for their anti-inflammatory toward IL-6 and TNF-α, antioxidant, as well as their anticancer activities against hepatic cancer cells. In addition, their anti-fungal and antibacterial activities against both Gram-positive and Gram-negative bacteria were tested. All the tested compounds have exhibited excellent (3a, d, e) to moderate anti-inflammatory activity. Additionally, esters (3b, f) and nitrile (2) showed excellent antioxidant activity. Furthermore, ester 3f, with isopropyl ester, exhibited the highest cytotoxic activity compared to the other esters. Moreover, all compounds were evaluated as selective inhibitors of the human COX-1 enzyme using molecular docking by calculating the free energy of binding, inhibition constant, and other parameters to find out the binding affinity. The molecular study showed that esters (3d, f) and nitrile (2) revealed the highest binding affinities, hence enhancing the inhibition activity with the active site of the COX-1 enzyme. All the tested compounds have more negative Gibbs free, electrostatic, and total intermolecular energies than the standard inhibitor ASA. These results indicate that, all the tested sultams are potent anti-inflammatory drugs as compared to standard inhibitors. Finally, the chemical properties and the quantum factors of synthesized sultams were calculated based on density functional theory (DFT) to predict reactivity, and then correlated with the experimental data. Ester 3f showed the lowest ionization potential and lowest energy gap (E_gap = 7.5691 eV), which was correlated with its cytotoxic activity. Furthermore, the spatial electron distribution of HOMO, LUMO were computed and it clearly indicates the electron donation ability of all the tested compounds.     

新型依布硒啉类MetAP2酶抑制剂的合成、分子对接与抑癌活性

以2-氯硒基-苯甲酰氯（1）为原料,在二氯甲烷溶液中与不同类型的胺（2a~2r）反应,合成了18个依布硒啉衍生物3a~3r(3i为新化合物),其结构经¹H NMR, ¹³C NMR和HR-MS(ESI)表征。利用分子对接技术预测了化合物3a~3r与甲硫氨酸氨肽酶2（MetAP2）5D6E蛋白的亲和活性,并采用MTT法研究了化合物对食管癌细胞（EC109）的体外增殖抑制活性。结果表明：浓度为100 μg·mL^-1时,2-(2-氯乙氧基-乙基)-1,2-苯并异硒唑-3(2H)-酮（3r）对EC109的增殖有良好的抑制活性,抑制率32%。     

Synthesis,Antifungal Activity, 3D-QSAR,and Molecular Docking Study of Novel Menthol-Derived 1,2,4-Triazole-thioether Compounds

A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 μg/mL, some of the target compounds exhibited good inhibitory activity against the tested fungi, especially against Physalospora piricola. Compounds 5b (R = o-CH₃ Ph), 5i (R = o-Cl Ph), 5v (R = m,p-OCH₃ Ph) and 5x (R = α-furyl) had inhibition rates of 93.3%, 79.4%, and 79.4%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Compounds 5v (R = m,p-OCH₃ Ph) and 5g (R = o-Cl Ph) held inhibition rates of 82.4% and 86.5% against Cercospora arachidicola and Gibberella zeae, respectively, much better than that of the commercial fungicide chlorothalonil. Compound 5b (R = o-CH₃ Ph) displayed antifungal activity of 90.5% and 83.8%, respectively, against Colleterichum orbicalare and Fusarium oxysporum f. sp. cucumerinum. Compounds 5m (R = o-I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, against F. oxysporum f. sp. cucumerinu, Bipolaris maydis and C. orbiculare. Furthermore, compound 5b (R = o-CH₃ Ph) showed the best and broad-spectrum antifungal activity against all the tested fungi. To design more effective antifungal compounds against P. piricola, 3D-QSAR analysis was performed using the CoMFA method, and a reasonable 3D-QSAR model (r² = 0.991, q² = 0.514) was established. The simulative binding pattern of the target compounds with cytochrome P450 14α-sterol demethylase (CYP51) was investigated by molecular docking.     

Synthesis,Characterization, Molecular Docking,and Antimicrobial Activity of New Arylidene-Substituted Imidazoles

Russian Journal of General Chemistry - The title compounds are synthesized by condensation of 2-[4-(arylidene)-5-oxo-4, 5-dihydrooxazol-2-yl]phenylacetate with aromatic amines in presence of the...     

Novel Etodolac-Based 1,2,4-Triazole Derivatives as Antimicrobial Agents: Synthesis,Biological Evaluation,and Molecular Docking Study

Russian Journal of Organic Chemistry - A series of novel 1,2,4-triazole nonsteroidal anti-inflammatory drugs (NSAIDs) derived from etodolac were designed and synthesized. The synthesized compounds...     

Synthesis,In vitro Coagulation Activities and Molecular Docking Studies on Three L-Histidine Amide Derivatives

Three novel L-histidine amide derivatives were synthesized and the corresponding chemical structures were characterized by means of melting point analysis, IR, MS, ¹H NMR as well as ¹³C NMR. The coagulation acti- vities of the compounds were evaluated by an MOE(molecular operating environment) docking technique and coagulation test. The results obtained from molecular docking show that the interactions between the compounds and thrombin exhibit procoagulant activity in combination with an improved combinatory effect. Moreover, the results of in vitro coagulation tests show that the L-histidine amide derivatives feature coagulant activities in common coagulation pathways. Compared with the blank control group, the optimal shortening rates of compounds 1―3 were 39.08%(0.5 mmol/L), 22.94%(1.0 mmol/L) and 15.38%(0.0625 mmol/L), respectively.     

Synthesis of Copper Oxide-Based Nanoformulations of Etoricoxib and Montelukast and Their Evaluation through Analgesic,Anti-Inflammatory,Anti-Pyretic,and Acute Toxicity Activities

Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.     

New Pyridopyrimidone Derivatives: Synthesis,Molecular Docking Studies,and Potential Anticancer Activity

Russian Journal of General Chemistry - A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer...     

Synthesis of Novel Benzofuran Based 1,2,3-Triazoles,Their Antimicrobial and Cytotoxic Activities,and Molecular Docking Studies

Russian Journal of General Chemistry - A series of novel {5-[(1H-1,2,3-triazol-4-yl)methoxy]-3-methylbenzofuran-2-yl}(phenyl)methanone derivatives has been synthesized with high yields,...     

含均三唑环的新型联苯四唑衍生物的合成及抗菌活性

通过4-芳基-5-(4-吡啶基)-1,2,4-三唑-3-硫醇(1)和2-三苯基甲基-5-(4′-溴甲基联苯-2-基)-四唑(5)反应, 制得一系列新的S-烷基化产物(6), S-烷基化产物在酸性条件下脱保护, 得到了14个未见文献报道的含1,2,4-三唑类联苯四唑(7a～7n)衍生物. 结构经元素分析, IR, NMR及FAB-MS确认. 对大肠杆菌、链球菌、枯草杆菌、金黄色葡萄球菌初步抑菌试验证明, 多数化合物表现了较好的抑菌活性.     

Synthesis,Crystal Structure,Fungicidal Activities and Molecular Docking of Acyl Urea Derivatives Containing 2-Chloronicotine Motif

Eighteen new acyl urea derivatives containing 2-chloronicotine moiety were synthesized using2-chloronicotinic acid as starting material via 4 steps conveniently.These 2-chloronicotine acyl urea structures were confirmed by ¹H NMR,¹³C NMR and HRMS.Compound 4r was further confirmed by X-ray diffraction.It crystallizes in the orthorhombic system,space group Pbca with a=7.2960（3）,b=14.8546（6）,c=25.2840（11）?,V=2740.3（2）?³,Z=8,the final R=0.0442 and w R=0.1033 for 4028...     

Synthesis,Biological Activity,and Molecular Docking Assessment of Some New Sulfonylated Tetrazole Derivatives

The designed molecular structures have been subjected to computational analysis for calculating their physicochemical properties and drug likeness. The calculated data indicate that most of the compound possess the bioactivity score in the active zone. Synthetic approach to the target compounds is straightforward and easy to handle. Structures of the new compounds are supported by FT-IR, ¹H, and ¹³C NMR, and mass spectra. Antimicrobial tests of the products against pathogens (S. aureus, S. epidermidis, E. coli, and P. mirabilis) indicate the products as active or highly active. Their cyto-toxicity is determined to be 92–98% at concentration of 3.125 µmol/L. The molecular docking analysis carried out for the target compounds against the receptor Glc-N-6P exhibits low binding energy and various binding sites of those.

     

New Chalcone Derivatives with Schiff Base-Thiophene: Synthesis,Biological Activity,and Molecular Docking Studies

Russian Journal of General Chemistry - New thiophene chalcones 3, 6 and thiophene Schiff base-chalcone derivatives 4a–4d, 7a–7d are synthesized. Structures of the compounds are...     

Phosphoryl Analogs of Salicylic Acid: Synthesis and Analgesic and Anti-Inflammatory Activity

The synthetically convenient method of preparation of unexplored phosphoryl analogs of salicylic acid (2-hydroxyphenylphosphonic and 2-hydroxyphenylphosphinic acids) has been developed for the search of novel nonsteroidal anti-inflammatory drugs. It has been shown that 2-hydroxyphenylphosphinic acid is a lowtoxic compound (LD₅₀ 3500 mg/kg) exhibiting analgesic activity significantly higher than both 2-hydroxyphenylphosphonic acid and the reference compound (sodium metamizole).     

New Thiazole-Bearing Oxadiazole Derivatives: Synthesis,Thymidine Phosphorylase Inhibitory Potential,and Molecular Docking Study

Russian Journal of Organic Chemistry - A series of sixteen oxadiazole derivatives containing a thiazole ring were synthesized, characterized by different spectroscopic techniques (1H and 13C NMR,...     

Synthesis and Anti-Inflammatory Activities of Some Novel S-Pyridyl Glycosides Derivatives

A series of some new acetylated S-glycosides of pyridine-2-thione derivatives, including D-glucose, D-galactose, D-xylose and L-arabinose derivatives were synthesized. Oxidation of some formed S-glycosides derivatives with H₂O₂ afforded the corresponding sulfones. S-Alkylation of pyridine-2-thione derivatives was performed to furnish the S-acyclo deazauridine derivatives. The entire tested compound showed potent anti-inflammatory activity were potent against edema and in the same time inhibited the prostaglandine formation. It is work mention that all the tested compounds showed high safety margin. The structures of the new synthesized compounds have been proved by IR, ¹ HNMR, mass spectra and elemental analysis.     

Synthesis,Antimicrobial Activity and Molecular Docking Study of Thiazole Derivatives

The reaction of 4‐thiochromane thiocarbohydrazone with a series of hydrazonoyl halides in dioxane in the presence of triethylamine afforded novel thiochromane derivatives incorporating 1,3‐thiazole moiety. The structure of the latter compounds was established by elemental analysis and spectral technique and by their chemical transformation. Moreover, the antimicrobial activity of the newly synthesized compounds was screened and the results showed that some compounds have higher activity than the applied fungicide and bactericide. The antimicrobial activity of the most active compounds was interpreted by molecular docking study.