Medicinal Chemistry

A novel series of N-(6,7-dimethoxynaphthalen-yl)sulfamide derivatives, targeting to angiogenesis and tumor growth, were well synthesized. Of these compounds, XGS-15 exhibited potent inhibitory effect on the proliferation of HCT116, PLC, U266, ES-2 and HEPG-2 cells and excellent anti-angiogenesis activity in both human umbilical vein endothelial cell (HUVEC) tube formation assay and the rat thoracic aorta rings test. Besides, compound XGS-15 showed weak inhibitory effects on human umbilical vein endothelial cell with high IC50 (>200 μM). So we speculated that compound XGS-15 revealed selective cytotoxic effect on tumor cells without influencing normal cells at low micromole ranges.

In the present study three piperine analogs of dipeptidyl boronic acid (1 to 3) were synthesized and evaluated the antimicrobial and anticancer activities. Chemical structures of the synthesized compounds were characterized by 1H, 13C and mass spectral studies. All the compounds were screened for their antineoplastic activity on HeLa cervical, MCF-7 breast and MIA PaCa-2 pancreatic cancer cell lines and antimicrobial activity against seven bacterial and five fungal species. In vitro results showed that most of the compounds displayed moderate to good inhibitory activity on the tested cancer cell lines, among them compound 1 showed good anticancer activity where as Compound 3 was found to be potent antimicrobial agent against Asperigillus fumigates at a concentration of 62 μg/mL than other tested compounds and the parent molecule piperine. All the compounds were subjected to molecular docking studies on Leucyl-tRNA synthase as well as for 20S proteasome inhibition. In silico molecular docking results demonstrated that all compounds had low binding energy toward the active pocket and thus they may act as a good Leucyl-tRNA synthase inhibitor.

All-trans-retinoic acid (ATRA), an active metabolite of vitamin A, is known to affect cell differentiation, proliferation, and development. Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The aim of this study is to assess the effects of ATRA against bleomycin-induced pulmonary fibrosis in rats. Animals were intratracheally instillated with bleomycin and/or intraperitoneally administered with ATRA. On day 28, rats were sacrificed and histological changes in the lungs were evaluated. Moreover, malondialdehyde (MDA) content, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in serum and lung, were achieved. Results displayed that rat body weight decreased while fibrosis score and inflammatory index in lung tissue were significantly increased, after bleomycin instillation. Administration of bleomycin followed by ATRA reduced bleomycin–induced weight loss, decreased the lung index and the inflammatory indices. Histopathological examination confirmed the antifibrotic effect of ATRA which apparently attenuated the degree of pulmonary fibrosis. In addition, data showed that ATRA significantly increased SOD, CAT and GPx levels as compared to bleomycin group (G2) concomitant to the decrease of MDA content in lung homogenates. These findings indicate that ATRA treatment significantly attenuated the increased pulmonary damage induced by bleomycin.

A series of thienopyrimidine oxadiazolederivatives (5a-l) were synthesized by cyclic condensation of substituted aroylhydrazides with triazole of carboxylic acid (4a-c). The synthesized compounds were characterized on the basis of their spectral (IR, 1H and 13C NMR) data and screened for antimicrobial activity where compounds 5b and 5d showed significant activity.

Silkworms are drawing international scientific attention owing to their significant hypoglycemic activity, attributed to 1-deoxynojirimycin (DNJ), which they obtain from eating mulberry leaves. DNJ content in silkworms varies significantly during its life cycle as a holometabolic insect. The effect of metamorphosis and molting on DNJ accumulation remains unclear, however. More knowledge is needed about DNJ dynamics during the silkworm life cycle given their potential use as a functional food with hypoglycemic effect. This paper aims to elucidate the DNJ dynamics of silkworms over their life cycle. We propose the best physiological stage for silkworm harvesting in consideration of DNJ production. The effect of metamorphosis and molting on DNJ accumulation is also discussed. Samples from key physiological stages of silkworms were collected and the DNJ content analyzed by reverse-phase high-performance liquid chromatography (RP-HPLC). We observed fluctuations in DNJ levels depending on the physiological stage of the silkworm. A higher level of DNJ was found in the molted larvae than the molting ones. The highest DNJ level was detected in the molted larvae of instar III (5.46 mg/g) in terms of bodyweight, while a silkworm from Day 3 of instar V possesses the highest level of DNJ (1512.46 μg per silkworm). These results imply that natural physiological changes in the silkworm, including molt and metamorphosis, affect DNJ accumulation significantly. The period from Day 3 to Day 4 of the 5th instar is considered the best time for silkworm harvesting given both DNJ concentration and silkworm biomass.

Pyrido [1,2-a] pyrimidine ring structure is one of the most interesting heterocycles in drug design and its derivatives have various potential pharmacological activities. An interesting approach of synthesizing a new series of pyridopyrimidine derivatives containing Schiff bases of certain amino acids, as privileged moieties of expected high potential in the field of antibacterial and antitumor agents, were investigated that may provide a synergistic model. The new derivatives 1-6 were synthesized by reacting 3-formyl-2H-pyrido [1, 2-a] pyrimidine-2, 4 (3H)-dione 1b with glycine, alanine, glutamic acid, histidine, tryptophan or leucine in methanol under reflux using glacial acetic acid as catalyst. The chemical structures of the new compounds and their intermediates (1-6, 1a and 1b) were characterized, identified and confirmed by spectral analysis (IR, 1H-NMR) and elemental microanalysis (CHN) and the results were within the acceptable limits. Disc-diffusion method was used to evaluate the antimicrobial activities of the newly synthesized compounds of interest 1-6, using Pseudomonas aurginosa, Staphylococcus aurueus, Bacillus subtilus, Candida albicans and Escherichia coli. The synthesized compounds 1-6 showed variable antibacterial activities ranged between good to moderately active, when compared with standards (amoxicillin and ceftriaxone). Compounds 4-6 also showed antifungal activities. However, compounds 5 and 6 are the most potent and have promising results. Compound 6 showed a good activity against all bacterial strains and fungi tested, while compound 5 showed the highest activity against Pseudomonas auroginosa. This approach has afforded the synthesis of new pyrido-pyrimidine derivatives containing Schiff bases of certain amino acids of reasonable and promising antibacterial activities.

The extensively clinical use of triazole-based medicinal drugs has been promoting increasing effort to develop new structural triazole derivatives. Benzotriazoles as fused aromatic nitrogen heterocycles of benzene ring with triazole exhibit wide potentialities in medicinal chemistry since some anticancer benzotriazole compounds like vorozole and 4,5,6,7-tetrabromo-1H-benzotriazole (TBB) were used in clinical therapy. The benzotriazole related investigations are becoming increasingly active. On the basis of authors’ researches and other literature in recent five years, this work for the first time gave a comprehensive review on the latest and outstanding developments of benzotriazole compounds in medicinal chemistry, including as anticancer, antifungal, antibacterial, antitubercular, antiviral, antioxidative, antiparasitic, antioxidative agents and so on. Hopefully, this contribution will be helpful to develop benzotriazole-based drugs with high bioactivity and low toxicity.

Gallic acid, a widely distributed phenolic acid present in various plant species, has been demonstrated to possess anti-inflammatory, antioxidant and anticarcinogenic properties. In this study, the protective effect of gallic acid on acute liver injury induced by dimethylnitrosamine in mice was investigated. We attempted to explore the molecular mechanism from a perspective of phase âÂ…¡ enzymes, which plays a crucial role in cellular defense against oxidative stress. Toxicant caused severe hepatic pathological damage and significant increase of serum transaminase levels. Hepatic lipid peroxidation and the glutathione depletion could also be observed after dimethylnitrosamine administration. Pretreatment of gallic acid at different doses could inhibit hepatic submassive necrosis and attenuate all the marker parameters in both serum and liver tissue. Administration of gallic acid was found to increase the expression level of heme oxygenase-1 (HO-1) and glutathione-s- transferase alpha 3 (GSTA3), thereby enhance the detoxication ability in liver tissue. The upregulation of phase âÂ…¡ enzymes is caused, at least in part, by the nuclear accumulation of Nrf2, a transcriptional factor which binds to the antioxidant response element of DNA and triggers the expression of phase âÂ…¡ enzymes. These findings provide further insight of hepatoprotection mediated by gallic acid.

Dengue and chikungunya are transmitted by Aedes aegypti and for controlling these diseases, the vector mosquito has to be controlled. Extensive use of synthetic and chemical insecticides has resulted in environmental hazards and also in development of physiological resistance among vector mosquito species. Plant products are considered to be a potential alternative approach as they are environmentally safe, target specific and biodegradable. In the present study, the crude chloroform, methanol and aqueous flower extracts of Jasminum officinale, Jasminum auriculatum and Jasminum grandiflorum were tested for the larvicidal efficacy against the third instar larvae of Aedes aegypti at concentrations of 62.5, 125, 250, 500, 1000, 2000, 4000 and 8000 mg/L. Mortality was recorded after 24 and 48 h. Amongst the extracts of Jasminum species tested, the crude chloroform flower extract of Jasminum grandiflorum was found to be effective showing 100% mortality at 1000 mg/L with LC50 value of 344.01 and 300.47 after 24 and 48 h respectively followed by the crude methanolic flower extracts of Jasminum officinale and Jasminum auriculatum. Further investigations are needed to elucidate the larvicidal activity of Jasminum grandiflorum crude chloroform flower extract against a wide range of all stages of mosquito species and also the active ingredient(s) of the extract responsible for larvicidal activity should be identified.