Antiangiogenic,anti-inflammatory and their antioxidant activities of Turnera subulata Sm. (Turneraceae)

Turnera subulata is a substantial medicinal plant used in folk medicine to treat various ailments. The current study was assess the total phenolic and flavonoid contents to evaluate the antioxidant and anti-inflammatory activities of the sequentially extracted T. subulata plant samples. In vitro anti-angiogenic activity was evaluated by chick chorioallantoic membrane (CAM) model for chloroform, ethyl acetate and ethanol extracts. The results obtained revealed that total phenolic content of the chloroform extract (24.13 ± 0.27 mg/g) and total flavonoid content (TFC) of the chloroform extract (22.28 ± 0.40 mg/g) were found to be suggestively higher than the other extracts. A strong antioxidant property was observed for all the six extracts. A study anti-inflammatory activity was observed in chloroform and ethanol extracts, with IC₅₀ ranging from 79 ± 1.01 μg/mL to 81 ± 1.01 μg/mL for protein denaturation assay and from 74 ± 0.11 μg/mL to 76 ± 1.11 μg/mL for HRBC membrane stabilization assay, respectively. The chloroform and ethanol extracts have exhibited good antiangiogenic property. Eventually, these results justified that the chloroform and ethanol extracts of T. subulata with great antioxidant, anti-inflammatory and antiangiogenesis potentials could be promising candidates for the development of a cost effective, potent anticancer drug with minimal side effects.     

Gas-chromatographic separation of tri(hetero)halogenomethane enantiomers

Five-atomic tri(hetero)halogenomethanes represent the simplest class of non-isotopic small chiral molecules suitable for the study of fundamental aspects of chirality. The analytical gas-chromatographic separation of the enantiomers of bromochlorofluoromethane 1 and of chlorofluoroiodomethane 2 on the immobilized chiral stationary phase octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-gamma-cyclodextrin 3, chemically linked to polydimethylsiloxane, is described. By temperature-dependent thermodynamic measurements very low isoenantioselective temperatures T(iso) are found and for optimum enantiomeric separations cryogenic temperatures are required. The ee values of enantiomerically enriched tri(hetero)halogenomethanes 1 and 2 are determined and relative configurations are correlated with the chromatographic elution order of 1 and 2 on 3.     

Synthesis and anti-inflammatory activity of 2-(2-aroylaroxy)-4,6-dimethoxy pyrimidines

Abstract-Reaction of 6a–f individually with 2-methylsulfonyl-4,6-dimethoxypyrimidine yielded 7a–f in excellent yield. The newly synthesized heterocycles were characterized by IR, ¹H NMR, and mass spectral data. Compounds 7a–f was screened for their anti-inflammatory activity and were compared with standard drugs. Of the compounds studied, the compound 7e showed more potent activity than the standard drugs at all doses tested.     

The significance of N-methylpicolinamides in the development of anticancer therapeutics: Synthesis and structure-activity relationship (SAR) studies

Cancer is the second most important cause of death worldwide. There is always a demand for new anticancer drugs and continuously a wide variety of natural and synthetic compounds were developed by the researchers. Nowadays, a large number of drugs in clinical practice were found to have a high incidence of side effect and multidrug conflict. The development of novel less toxic, low cost and very energetic N-methylpicolinamide-bearing hybrids is a hot research topic in the community of medicinal chemistry. Herein we highlight the current advances in the synthesis of picolinamide-containing heterocyclic compounds as potent anticancer agents. In addition, briefly explore their structure-activity relationship studies for the inspiration of the innovation and development of more potent and effective drugs against various death-causing cancer diseases.     

New cannabidiol (CBD) derivatives: Synthesis,anti-inflammatory activity,and molecular docking

A series of new cannabidiol (CBD) derivatives were synthesized by employing hydrogenation reaction and click chemistry. Then, the cytotoxicity and anti-inflammatory activities of cannabinoid derivatives were determined. Compound 14 was found to have low cytotoxicity and high anti-inflammatory activity, and the anti-inflammatory mechanism of compound 14 was preliminarily explored, which inhibited the synthesis and release of the pro-inflammatory cytokine TNF-α. The experimental results were confirmed by docking analysis. The water solubility of compound 14 was determined. Based on the results, the structure-activity relationships (SARs) of the CBD derivatives were discussed for exploring novel anti-inflammatory drugs.     

New benzimidazothiazole derivatives as anti-inflammatory,antitumor active agents: Synthesis,in-vitro and in-vivo screening and molecular modeling studies

A new series of benzimidazothiazole derivatives has been synthesized. The structure of the products was confirmed by spectroscopic techniques such as IR, NMR and mass spectroscopy. The tested compounds were evaluated for their anti-inflammatory activity either in vitro through the COX enzyme inhibition assay, or in vivo through carrageenan paw edema technique. Results revealed that compound 25 and 29 represented the most active ones among the entire series with % inhibition 72.19, 72.07 for COX-1, and 87.46, 87.38 for COX-2, respectively. Interestingly, all synthesized compounds exhibited IC₅₀ values less than both reference drugs celecoxib and naproxen, indicating their superior potency. For compound 25, it showed about 340 and 198 times more potent than celecoxib and naproxen respectively as COX-1 inhibitor (IC₅₀ value 0.044 vs. 15.000 and 8.700 µM), and 10 and 115 times more potent than the same drugs as COX-2 inhibitor (IC₅₀ value 4.52 vs. 40.00 and 520.00 nM). The antitumor activity of the products was also evaluated and the results obtained are consistent with those obtained by the anti-inflammatory screening where compounds 25 and 29 proved to be the most active ones among the other compounds with %GI ranging from 31.5 to 62.5% and they exhibited the lowest IC₅₀ values as well. The ADMET analysis of the tested compounds was also performed in addition to the molecular modeling studies that included flexible alignment, surface and electrostatic maps in addition to the Lipinisk's rule of five.     

Quantitative structure-activity relationship (QSAR) for neuroprotective activity of terpenoids

Neuroprotective activity of thirteen terpenoids on human neuroblastoma SH-SY5Y was evaluated in vitro by using a simulated ischemia model. The protective effects on ischemic damage ranged from 3.0% to 56.5%, and trans-4,11,11-trimethyl-8-methylenebicyclo[7,2,0]undec-4-ene (trans-caryophyllene) showed the highest neuroprotective activity. A quantitative structure-activity relationship (QSAR) model was developed for eleven terpenoids with significant neuroprotective activity using TSAR software. The QSAR study produced two equations with significant predictive values (r(2) and p value) and indicated that the activity was mainly governed by lipophilicity, shape index, and electrostatic property. This QSAR approach can contribute to a better understanding of structural properties of the terpenoids responsible for neuroprotection, and can be useful in predicting the neuroprotective activity of other terpenoids.     

Synthesis, cytotoxicity, and structure-activity relationship (SAR) studies of andrographolide analogues as anti-cancer agent

A series of analogues of andrographolide, prepared through chemo-selective functionalization at C14 hydroxy, have been evaluated for in vitro cytotoxicities against human leukemic cell lines. Two of the analogues (6a, 9b) exhibited significant potency. Preliminary studies on structure-activity relationship (SAR) revealed that the α-alkylidene-γ-butyrolactone moiety of andrographolide played a major role in the activity profile. The structures of the analogues were established through spectroscopic and analytical data.     

Novel pyrimidine-pyridine hybrids: Synthesis,cyclooxygenase inhibition,anti-inflammatory activity and ulcerogenic liability

Some derivatives containing pyrido[2,3-d:6,5d′]dipyrimidine-4,5-diones (9a-f), tetrahydropyrido[2,3-d]pyrimidine-6-carbonitriles (11a-c) and 6-(4-acetylphenyl)-2-thioxo-2,3,5,6,7,8-hexahydro-1H-pyrimido[4,5-d]pyrimidin-4-one (12) were synthesized from 6-amino-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (8). The anti-inflammatory effect of these candidates was determined and the ulcer indices were calculated for active compounds. 7-Amino-5-(3,4,5-trimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-6-carbonitrile (11c) exhibited better edema inhibition than celecoxib. Moreover, compounds 9b, 9d and 11c revealed better COX-2 inhibitory activity in a range (IC₅₀ = 0.25–0.89 µM) than celecoxib (IC₅₀ = 1.11 µM). Regarding ulcerogenic liability, all of the compounds under the study were less ulcerogenic than indomethacin. Molecular docking studies had been carried on active candidates 9d and 11c to explore action mode of these candidates as leads for discovering other anti-inflammatory agents.     

Synthesis, screening and quantitative structure-activity relationship (QSAR) studies of some glutamine analogues for possible anticancer activity

We described the syntheses, biological activities and QSAR studies of 36 new 5-n-substituted-2-(substituted benzenesulphonyl) glutamines 6-41 with different substitutions. These compounds were designed as structural analogues of most reactive amino acid, 'glutamine' (GLN), especially in the tumor cells. They present the new basic lateral chains at R(5) position as well as different substitutions at 2', 3', 4', and 5' positions on the benzene ring. The synthesized compounds have been tested for antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice using percentage inhibition of tumor weight as inhibitory parameter. In order to elucidate the structural requirements for antitumor activity, quantitative structure-activity relationship (QSAR) studies have been performed using extra thermodynamic model of Hansch. QSAR equations showed that the electronic parameter (sigma) on the aromatic ring system, steric parameter (Es) and to some extent Sterimol length of the substituent (L) on the aliphatic side chain correlate significantly with the antitumor activity. Resonance factor occupies the major electronic contribution on the aromatic ring system to the activity.     

Anti-inflammatory and antimicrobial activities of novel pyrazole analogues

A new sequence of pyrazole derivatives (1–6) was synthesized from condensation technique under utilizing ultrasound irradiation. Synthesized compounds were characterized from IR, ¹H NMR, ¹³C NMR, Mass and elemental analysis. Synthesized compounds (1–6) were screened for antimicrobial activity. Among the compounds 3 (MIC: 0.25 μg/mL) was exceedingly antibacterially active against gram negative bacteria of Escherichia coli and compound 4 (MIC: 0.25 μg/mL) was highly active against gram positive bacteria of Streptococcus epidermidis compared with standard Ciprofloxacin. Compound 2 (MIC: 1 μg/mL) was highly antifungal active against Aspergillus niger proportionate to Clotrimazole. Synthesized compounds (1–6) were screened for anti-inflammatory activity and the compound 2-((5-hydroxy-3-methyl-1H-pyrazol-4-yl)(4-nitrophenyl)methyl)hydrazinecarboxamide (4) was better activity against anti-inflammatory when compared with standard drugs (Diclofenac sodium). Compounds (2, 3 and 4) are the most important molecules and hence the need to develop new drugs of antibacterial, antifungal and anti-inflammatory agents.     

Identification and preliminary structure-activity relationship studies of novel pyridyl sulfonamides as potential Chagas disease therapeutic agents

Chagas disease is a neglected pathology responsible for about 12,000 deaths every year across Latin America. Although six million people are infected by the Trypanosoma cruzi, current therapeutic options are limited, highlighting the need for new drugs. Here we report the preliminary structure activity relationships of a small library of 17 novel pyridyl sulfonamide derivatives. Analogues 4 and 15 displayed significant potency against intracellular amastigotes with EC₅₀ of 5.4?µM and 8.6?µM. In cytotoxicity assays using mice fibroblast L929 cell lines, both compounds indicated low toxicity with decent selectivity indices (SI) >36 and?>23 respectively. Hence these compounds represent good starting points for further lead optimization.     

2,2',4-trihydroxybenzophenone: crystal structure, and anti-inflammatory and antioxidant activities

The crystal structure of '2,2',4-trihydroxybenzophenone' (=(2,4-dihydroxyphenyl)(2-hydroxyphenyl)methanone; 1) was determined, and its molecular structure, along with intra- and intermolecular H-bonds, was analyzed. The anti-inflammatory potential of 1, evaluated by means of the rat-paw-edema assay, with carrageenan as inflammation stimulus, was found to be similar high as that of indomethacin. In contrast, benzophenone proper (2) was hardly active in this assay. Our results indicate that these anti-inflammatory effects are related to the action of kinins and prostaglandins. The radical-scavenging properties of 1 towards DPPH were found to be similar as those of typical phenolics, but somewhat lower than that of ascorbic acid. The structure-activity relationship (SAR) of 1 is discussed.     

Synthesis, biological evaluation and molecular docking studies of stellatin derivatives as cyclooxygenase (COX-1, COX-2) inhibitors and anti-inflammatory agents

Stellatin (4), isolated from Dysophylla stellata is a cyclooxygenase (COX) inhibitor. The present study reports the synthesis and biological evaluation of new stellatin derivatives for COX-1, COX-2 inhibitory and anti-inflammatory activities. Eight derivatives showed more pronounced COX-2 inhibition than stellatin and, 17 and 21 exhibited the highest COX-2 inhibition. They also exhibited the significant anti-inflammatory activity in TPA-induced mouse ear edema assay and their anti-inflammatory effects were more than that of stellatin and indomethacin at 0.5 mg/ear. The derivatives were further evaluated for antioxidant activity wherein 16 and 17 showed potent free radical scavenging activity against DPPH and ABTS radicals. Molecular docking study revealed the binding orientations of stellatin and its derivatives into the active sites of COX-1 and COX-2 and thereby helps to design the potent inhibitors.     

Macrocyclic copper(II) complexes: superoxide scavenging activity, structural studies and cytotoxicity evaluation

Synthetic superoxide dismutase mimetics have emerged as a potential novel class of drugs for the treatment of oxidative stress related diseases. Among these agents, metal complexes with macrocyclic ligands constitute an important group. In this work we synthesized five macrocyclic copper(II) complexes and evaluated their ability to scavenge the superoxide anions generated by the xanthine-xanthine oxidase system. Two different endpoints were used, the nitro blue tetrazolium (NBT) reduction assay (colorimetric method) and the dihydroethidium (DHE) oxidation assay (fluorimetric method). IC(50) values in the low micromolar range were found in four out of five macrocyclic complexes studied, demonstrating their effective ability to scavenge the superoxide anion. The IC(50) values obtained with the NBT assay for the macrocyclic copper(II) complexes, were consistently higher, approximately threefold, than those obtained with the DHE assay. Spectroscopic and electrochemical studies were performed in order to correlate the structural features of the complexes with their superoxide scavenger activity. Cytotoxicity assays were also performed using the MTT method in V79 mammalian cells and we found that the complexes, in the range of concentrations tested in the superoxide scavenging assays were not considerably toxic. In summary, some of the presented macrocyclic copper(II) complexes, specially those with a high stability constant and low IC(50), appear to be promising superoxide scavenger agents, and should be considered for further biological assays.     

一些裸子植物鲜叶提取物清除自由基的活性研究

用二苯基苦基苯肼自由基酶标仪法,对常见的60余种裸子植物鲜叶的自由基清除活性进行了比较.发现不同科属,不同树种鲜叶的80%甲醇提取物的自由基清除活性有很大差异,其中罗汉松科罗汉松属树木鲜叶在浓度在0.5mg/mL,于37℃下孵育20min时的自由基清除率平均可达55.9%,而柏科侧柏属平均仅为7.1%;罗汉松,孔雀柏、小叶罗汉松、湿地松、杉木和刺柏等鲜叶有很强的自由基清除活性,它们的自由基清除率分别可达61.1%,58.4,57.6%,57.1%,51.8%和50.4%,表明这些树种有较大的开发潜力。     

Design,synthesis of 2,3-disubstitued 4(3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents: COX-1/2 inhibitory activities and molecular docking studies

A new series, 2-substituted mercapto-3-[2-(pyridin-2-yl)ethyl]-4(3H)-quinazolinone 1–21, was synthesized and evaluated for in vivo anti-inflammatory and analgesic activities and in vitro COX-1/COX-2 inhibition. Compounds 1, 4, 5, 6, 8, 10, 13, 14, 15, 16, and 17 exhibited potent anti-inflammatory and analgesic properties, with ED₅₀ values of 50.3–112.1 mg/kg and 12.3–111.3 mg/kg, respectively. These values may be compared with those of diclofenac sodium (ED₅₀ = 112.2 and 100.4 mg/kg) and celecoxib (ED₅₀ = 84.3 and 71.6 mg/kg). Compounds 4 and 6 possessed strong COX-2 inhibitory activity with IC₅₀ (0.33 μM and 0.40 μM, respectively) and selectivity index (SI > 303.0 and >250.0, respectively) values that are similar to those of the reference drug celecoxib (IC₅₀ 0.30 μM and COX-2 SI > 333). Compounds 5, 8, and 13 demonstrated effective COX-2 inhibitory activity with IC₅₀ values of 0.70–0.80 μM and COX-2 SI > 125–142. Potent COX-2 inhibitors, such as compounds 4, 6, and 13, were docked into the active site pockets of COX-1 and COX-2, with the greatest recognition occurring at the COX-2 binding site and insignificant interactions at the binding site of the COX-1 pocket.     

Synthesis and structure-activity relationship (SAR) study of 4-azabenzoxazole analogues as H3 antagonists

The synthesis and SAR of a novel series of 4-azabenzoxazole histamine H(3) antagonists is described. Introduction of substituted phenyl, pyridyl and fused heterocyclic groups to the 6-position of the 4-azabenzoxazole core gave a series of compounds with good H(3) antagonist activity in both ex vivo and in vivo assays.     

Synthesis,anti-inflammatory activity and modeling studies of cycloartane-type terpenes derivatives isolated from Parthenium argentatum

The 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema model in mice determined the anti-inflammatory activities in vivo of argentatins A, B and D, the main cycloartenol-type triterpenes present in Parthenium argentatum. Our results showed that argentatin B (ED₅₀ = 1.5 × 10⁻⁴ mmol/ear) and argentatin A (ED₅₀ = 2.8 × 10⁻⁴ mmol/ear) were more potent anti-inflammatory agents than indomethacin (ED₅₀ = 4.5 × 10⁻⁴ mmol/ear), the reference drug. Based on these findings, we decided to evaluate 13 derivatives of argentatins A and B. All the derivatives showed anti-inflammatory activity in the TPA-induced edema model in mice. The most active compound was 25-nor-cycloart-3, 16-dione-17-en-24-oic acid, obtained from argentatin A (ED₅₀ = 1.4 × 10⁻⁴ mmol/ear). Argentatin B was assayed as inhibitor of COX-2 activity one of the key enzymes involved in the TPA assay. The results showed that argentatin B at 15 μM doses inhibited 77% COX-2 activity. Docking studies suggest that argentatin B interacts with Arg 120, a key residue for COX-2 activity.