Medicinal Chemistry

A series of 1,3,5-triazines derivatives were designed, synthesized and evaluated their biological activity. The preliminary investigation showed that most compounds displayed good to excellent potency against seven tested cancer cell lines as compared with ZSTK474. Compounds 5a, 7a and 7d were further examined for their inhibitory activity against PI3Kα kinase. The most promising compound 7d (PI3Kα half-maximal inhibitory concentration [IC50] = 10.56 nM) showed remarkable cytotoxicityagainst H1975, A549, PC9, HCT116, BT549, CNE2 and SW480 cell lines with IC50 values of 2.83 μM, 4.62 μM, 0.29 μM, 3.92 μM, 0.56 μM, 3.53 μM and 1.27 μM, respectively. The structure-activity relationships (SARs) analyses will guide us to further refine the structure of 1,3,5-triazines derivatives to achieve optimumanticancer activity.

Search of complementary and alternative medicine has gained a thrust in the recent decade due to the pronounced side effects and health hazards of the chemically synthesized drugs. Hereby, a comprehensive knowledge about the traditionally used medicinal plants is indispensable for exploration of its novel bioactive components. One of such comparatively less explored medicinal plant is Gnidia glauca. Although, it has folkloric, traditional phytomedicinal and agrochemical applications in various parts of the world, still there are no available scientific validations or evidences to support the fact. In African medicine it is used for treatment of abdominal pain, cancers, wounds, snake bites, sore throat and burns. It is also well known for its piscicidal, insecticidal, molluscicidal and even homicidal activity for its use as arrow poisons. Similarly, its antineoplasticactivity is reported to be remarkably superior. However, till date there are no comprehensive information on the plant. In view of the background, herein we present the first commentary on complete research carried out till date on G. glauca and its promises as complementary and alternative medicine.

A sesequiterpenoid, 2α-hydroxyl-3β-angeloylcinnamolide (HAC) was isolated from the Chinese medicinal herb Polygonum jucundum Lindex. (Polygonaceae) with anti-inflammatory activities in vivo. In the present study, we investigated the anti-inflammation effects of HAC on lipopolysaacharide (LPS)-induced murine RAW264.7 cells. As the results, we found that HAC dose-dependently decreased NO over-production with IC50 value of 17.68 μM but showed very weak inhibition on TNF-α release with IC50 value of 98.66 μM. Meanwhile, eight novel derivatives modified at C-2 position of HAC were synthesized to further explore the structure-activity relationships (SARs) of HAC on antiinflammation effects. Compound PJH-1, an acetyl easer of HAC, showed better inhibition on over-production of NO and TNF-α (IC50, 7.31 and 3.38 μM, respectively). Furthermore, we demonstrated that HAC and PJH-1 attenuates the mitogen-activated protein kinases (MAPK) signaling pathways through blocking the phosphorylation of ERK, p38, JNK/MAPK. We also found that the structure of PJH-1 are more stable than that of HAC in cell medium, these finding are useful to develop in vitro molecular mechanism research of HAC. In a conclusion, our studies enhance the understanding of anti-inflammation activities of HAC and lead to the discovery of novel derivatives as potential antiinflammation agents.

In 2012, a novel human coronavirus (CoV) associated with severe respiratory tract infection, Middle East Respiratory Syndrome (MERS-CoV) was first recognized and since then 1401 patients were infected across the world (26 countries) with this virus, 543 (~39%) of which died. The diseases present severe respiratory infection often with shock, acute kidney injury and coagulopathy. Its human-to-human transmission through close contact has raised a global concern about its potential pandemic. This review describes the strategies used to develop effective pharmacotherapeutics for MERS-CoV, which are based on the experience gained from SARS-CoV outbreak in 2003.

Synthetic chemistry is playing revolutionary role in human beings by synthesizing novel compounds by different techniques. The present study was designed to prepare bioactive compoundsand evaluate their antioxidantand enzyme inhibition studies. Metal complexes of cefixime were prepared by reacting metal salts of different transition metals with sodium salt of cefixime. Their characterization was done with melting point and FTIR studies which confirmed the synthesis of metal complexes. It was concluded from results that synthesized compounds showed very weak response against AChE and some extent to BChE. In contrast to esterase family protease was inhibited significantly and T4 exhibited more than 90% inhibition (93.2 ± 0.1%). Antioxidant study was conducted using well known DPPH free radical assay while enzyme inhibition potential was evaluated according to standard protocols. Maximum antiradical activitywas exhibited by T6 (80.84 ± 1.6%) with IC50 45 ± 2 μg/ml while T5 remained almost inactive. Antibacterial studies have been carried out against Escherichia coli and Bacillus subtilis.

Aristotelia chilensis (Maqui) is a native berry from Chile that has a wide range of biological actions. It is mainly composed of anthocyanins, indole alkaloidsand flavonoids. However, the high concentration of polyphenols has been identified as the main responsible for the anti inflammatory, analgesic and antioxidants effects of their extracts, juices and fruit. The nutraceuticals or functional foods development is an excellent opportunity to make a nutritious and healthy product. This review includes the chemical and nutritional characteristics of Maqui. The pharmacological and biological activities are included in this work. Also shows our need to develop new healthy products

Simple spectrophotometricmethod has been developed and validated for the determination of oxyfluorfen herbicide residues. The proposed method is based on the formation of an orange charge- transfer complex between oxyfluorfen pesticideas electron donor and 1,2- naphthoquinone-4-sulphonate (NQS) as electron acceptor. In basic medium pH 13.0, an orange colored product exhibiting maximum absorption peak (λ max) at 460 nm. The variables that affected the reaction such as pH, concentration and volume of NQS reagent, amount of buffer solution and reaction time were carefully studied and optimized. Under the optimum conditions, Beer’s law is obeyed in the range 0.4-4.0 μg/ mL of oxyfluorfen. The linear regression equation of the calibration curve is A=0.0906+0.2579 c (μg/mL), with a linear regression correlation coefficient of 0.9993. The molar absorptivity was 1.33 × 105 l/mol cm. The limits of detection (LOD) limits of quantification (LOQ) were found to be 0.12 μg/ mL, 0.36 μg/mL, respectively. The recovery rate is in the range of 93.50-103.00% was obtained. The proposed method has been successfully applied to the determination of oxyflourfen pesticide residues in tomato, onion and water with good accuracy and precision.

Natural or synthetic chalconeswith different substituents have revealed a variety of biological activities that may benefit human health. The underlying mechanisms of action, particularly with respect to the direct cellular targets and the modes of interaction with the targets, have not been rigorously characterized, which imposes challenges to structure-guided rational development of therapeutic agents or chemical probes with acceptable target-selectivity profile. This review summarizes literature evidence on chalcones’ direct molecular targets in the context of their biological activities.

Some novel B-norcholesteryl thiazole derivatives were synthesized and their structures were characterized by IR, NMR and HRMS. The antiproliferative activity of the compounds against human cervical carcinoma(HeLa), human lung carcinoma (A549), human liver carcinoma (HEPG2) and normal kidney epithelial (HEK293T) cells was assayed. The results revealed that compounds 14 and 17 with a structure of N-methylthiazole showed distinct antiproliferative activity against A549 and HEPG2 cells. Compounds 20-24 with a structure of N-phenylthiazole displayed a selective antiproliferativeactivity on HeLa cells and were almost inactive to normal kidney epithelial cells (HEK293T). The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.

Objective: In order to indicate the cross-resistance between rifampin (RFP) and rifabutin (RFB) in multi-drug resistant Mycobacterium tuberculosis (MDR-TB) clinical strains and to provide the laboratory data for using rifabutin in the treatment of MDR-TB.
Methods: The minimal inhibitory concentrations (MICs) of RFB and RFP in 7H10 Middlebrook medium against 99 MDR-TB clinical strains were determined by microplate assays.
Results: Among these 99 isolates, 85 were resistant to rifabutin at concentrations >0.5 μg/ml. The cross-resistance ratio between rifampin and rifabutin was 85.86%. The MICs of RFB were 8-32 times lower than those of RFP (χ²=125.905, p<0.001). The crossresistance ratio increased with the resistance level of RFP. The cross-resistance strains in the lower (the MICs of RFB 2 ~ 4 μg/ml) and the medium groups (the MICs of RFB 8 ~ 16 μg/ml) were 0/9 and 5/9 respectively, while in the high rifampin-resistant group (the MICs of RFB ≥ 32 μg/ml) almost all of the strains but one were cross-resistant (98.8%, 80/81).
Conclusion: RFB has the activities against MDR-TB clinical strains in vitro. The cross-resistance ratio between rifampin and rifabutin increased with the resistance level of RFP. RFB is one of alternativese for the treatment of MDR-TB.