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A series of Schiff bases derived from 4-methylsalicylic acid (4a–4s) were synthesized, 14 of which (4a–4h, 4j–4l, 4n, 4q, and 4s) were reported for the first time. All the synthesized compounds were evaluated for their immunosuppressive activities for the first time. Among them, compound 4o displayed the most potent biological activity against lymph node cells (IC50 = 1.02 μM for lymph node cells and IC50 = 2.17 μM for PI3Kγ). The results of apoptosis and western-blot assays demonstrated that the immunosuppressive activity of compound 4o might be mediated by the inhibition of PI3K/AKT signaling pathway. Docking simulation was performed to position compound 4o into the PI3Kγ structure active site to determine the probable binding model.

Drug discovery is a difficult task, and is even more challenging when the target evolves during therapy. Antiviral drug therapy is an excellent example, exemplified by the evolution of therapeutic approaches for treatment of hepatitis C and HIV-1. Nick Meanwell and his colleagues made important contributions leading to molecules for treatment of hepatitis C and HIV-1, each with distinct mechanisms of action. This review summarizes the discovery and impact of these drugs, and will highlight, where applicable, the broader contributions of these discoveries to medicinal chemistry and drug discovery.

A new synthesis of the thiepino[2,3-b]pyridine ring system 4 was achieved via intramolecular condensation of the 2-thiobutyrate ester nicotinonitrile derivative 6 with sodium hydride. Compound 6 was provided by alkylation of the nicotinonirile-2-thiol derivative 5 with ethyl 4-bromobutyrate in the presence of sodium carbonate. On attempting the previous alkylation in the presence of sodium hydride afforded the pyridoazepine 11 instead of thiepinopyridine 4 in one-pot synthesis. Computational quantum chemistry was utilized to explore the reaction route at the level of DFT. Data of the computational studies indicated that both anions of compounds 8 and 9 have the same stabilization energies. Antitumor activity evaluation, in vitro, of compound 4 showed high affinity as a potential novel antitumor lead.

Hydrodictyon reticulatum is used in traditional medicine in Mexico to decrease gastrointestinal disorders suggesting that some of its chemical components have properties that relax smooth muscle. The hexane extract showed the most promising biological effects, with IC50 of 49.34 μg/ml in the spontaneous contraction of ileum. A detailed phytochemical analysis of the hexane extract led to the isolation of the known sesquiterpenes: β-Cayophyllene-4,5-α-oxide (1) and two new sesquiterpene lactones, 3α,4α,8α-trihydroxy-10α-methoxy-1α,5α,7α,11βH-guaia,6α,12-olide (2) and 4α,8α-dihydroxy-10α-methoxy-1α,5α,7α,11-βH-guaia,6α,12- olide (3). The identification and characterization of these compounds were determined using 1-D and 2-D-NMR (through interpretation of NMR data). The antispasmodic activity of sesquiterpenes of H. reticulatum was studied on isolated tissue preparations from rabbit and rat intestine. The compounds at 1.79 at 3.44 × 10−8 M doses reduced acetylcholine (Ach), histamine, and barium chloride-induced contractions on isolated rat ileum. Therefore, possess similar relaxant mechanism of action, in view of the fact that sesquiterpenes inhibit K+-induced contraction and act through serotoninic, muscarinic, and histaminic receptors. So these data support that extract may interfere with calcium mobilization from intracellular stores or with calcium interaction with regular proteins or in the other steps in the calcium-signaling pathway.

This study aimed to evaluate the antioxidant effect and antibacterial activity of the triterpene 3β,6β,16β-trihydroxylup-20(29)-ene (CLF1) isolated from Combretum leprosum leaves on mature biofilms from Streptococcus mutans and S. parasanguinis, both involved in dental caries. In order to determine the bacterial death time curve promoted by CLF1, minimum inhibitory concentration and minimum bactericidal concentration were also assessed. The susceptibility of mature biofilms from both species to CLF1 was investigated through total biomass quantification and enumeration of biofilm-entrapped colony forming units. Moreover, the effect of CLF1 on S. mutans biofilm architecture was investigated by scanning electron microscopy. Additionally, the antioxidant properties of CLF1 were assessed by scavenging of 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) free radical, ferrous ion chelating assay, ferric-reducing antioxidant power, and β-carotene bleaching assay. The minimum inhibitory concentration and minimum bactericidal concentration of CLF1 for both species were 3.9 and 15.6 μg/mL, respectively, and no bacterial growth was detected at 24 h treatment. Moreover, CLF1 reduced the biomass and viability of biofilms from both species. Electron micrographs of S. mutans biofilms confirmed such results and showed damages on bacterial surface. Regarding antioxidant activity, CLF1 showed efficient antioxidant ability in scavenging DPPH radical and inhibiting β-carotene oxidation. In summary, CLF1 should be considered as an effective molecule against infections caused by S. mutans and S. parasanguinis biofilms, as well as a natural antioxidant.

3-D QSAR studies were conducted using a series of 39 compounds obtained in our laboratory to inhibit aminopeptidase N/CD13 (APN) for developing highly potent antitumor agents. Among constructed 3-D QSAR models, the best q 2 is 0.664 and the best r 2 is 0.995. Henceforth, the best 3-D QSAR model was applied for further chemical modification and optimization. Therefore, seven molecules were designed, and their activity values were predicted by the generated model. Their binding modes were elucidated by docking. Finally, both the high predicted activity values of the seven designed molecules and the favorable binding patterns emphasize the significance for further synthesis of these designed compounds.

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the rhizomes of Kaempferia parviflora Wall. ex Baker (Zingiberaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of dichloromethane fraction of K. parviflora rhizomes, we isolated sixteen compounds (1–16), including flavonoid derivatives (1–12), anthraquinones (13 and 14), triterpene (15), and triterpene glycoside (16). The structures of the isolated compounds were established in an extensive 1D and 2D NMR, as well as MS analysis. The sEH inhibitory activities of all isolated compounds were evaluated. Among the isolated flavonoid derivatives, 4, 6, 8, 10, and 12 were identified as potent inhibitors of sEH, with IC50 values ranging from 0.9 ± 0.1 to 4.5 ± 0.1 μM. In addition, a kinetic analysis of the flavonoid derivatives (1–12) revealed that the inhibitory activity of flavonoid derivatives 1–4 and 6–12 is mixed with K i values ranging from 0.1 ± 0.0 to 14.3 ± 0.3 μM, whereas compound 8 was a non-competitive with K i = 0.3 ± 0.0 μM. These findings suggest that flavonoid derivatives from K. parviflora rhizomes are potential novel sEH inhibitors.

The Murraya koenigii miraculin-like protein (MKMLP) has been shown to have unusual solubility and stability properties. Here, the conformational stability and the solubility of MKMLP were assessed in different physicochemical conditions. In solubility studies, the presence of salt helped in resolubilization of precipitated protein at low pH. 8-Anilino-1-naphthalene sulfonate (ANS) fluorescence studies showed that protein significantly unfolds at pH 2.0 and addition of salts helped in refolding of the protein with a recovery of inhibitory activity. In the presence of DTT, a substantial increase in ANS fluorescence was observed only when protein was incubated for more than 30 min in 100-mM DTT. MKMLP retained approximately 52% of inhibitory activity when incubated for 120 min in 100-mM DTT. A minor increase in fluorescence intensity was observed in presence of urea and guanidine hydrochloride, however, a significant amount of unfolding was observed in presence of high concentration of β-mercaptoethanol, SDS, and HCl.

A series of 8-benzyloxy-substituted quinoline ethers (2a–n) compounds were synthesized. All synthesized compounds were screened in vitro for their preliminary antimicrobial activities against two Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), two Gram-positive bacteria (Staphylococcus aureus and Staphylococcus epidermidis), and a fungal species (Aspergillus niger). Among all synthesized compounds, compound 2e showed a significant growth inhibitory activity with MIC value 3.125 μg/mL which was comparable to 8-hydroxyquinoline (2.5 μg/mL) and terbinafine (1.25 μg/mL) against A. niger.

A series of novel 2-substituted benzimidazole analogs has been designed and synthesized by connecting the benzimidazole nucleus with variedly substituted chalcone moieties through an amino linker. The designed analogs were predicted for their biological activity profile through the computer software PASS. The compounds were predicted to have potent anthelmintic activity. These were synthesized and the activity of each compound was evaluated experimentally at the concentrations of 0.1, 0.2, and 0.5 % in terms of mortality time and paralysis time for the helminthes. The experimentally observed activity was found to comply with the PASS predicted activity. All compounds showed dose-dependent activities. The compounds with an electron releasing group at the para position on phenyl ring in the chalcone moiety (8 and 9) were the most active in comparison to those bearing electron withdrawing groups. The corresponding ortho analogs (4 and 5) also revealed good paralytic and lethal activities. The higher activities of 8 and 9 may be attributed to the favorable electronic interactions of the electron releasing groups present at para position of the phenyl ring. Comparative analysis of the Lipinski’s parameters and the activities of the compounds revealed all the compounds to comply with the Lipinski’s rule of five. Further an optimum hydrophilicity and total polar surface area in the range of 65–80 of the molecule are required for the potent activity, but Molar refractance is not found to have any significant role in determining the anthelmintic activity.