Medicinal Chemistry

Malaria is a major health problem and Plasmodium falciparum strain resistance to existing antimalarials drugs made the current approach inadequate for treatment of malaria. Drug development directed against malaria is generally targeting blood schizonts. However, to prevent relapse, tissue schizontocides are recommended to clean residual infection in the tissues. In spite of the available drugs, malarial chemotherapy is still insufficient and therefore new strategies are being explored to fill the gaps. The new approaches are being used to generate new compounds as well as combinations of drugs for development of effective and safe antimalarial therapy. This review discusses the recent developments in 4-aminoquinoline derived new analogs and insight into design and development of new antimalarials.

Cucurbita pepo, is widely used like food and in folk medicine around of the world. This aims a comprehensive of the pharmacological, chemical constituents, and clinical uses. Also have been identified the medicinally important phyto-constituents belonging mainly to cucurbitosides, multiflorane-type triterpenoids, carotenoids, ent-kauranetype diterpene, and cucurbitaglycosides. Extracts and metabolites of this plant, particularly those from seeds and fruits possess useful pharmacological activities. A survey of the literature shows C. pepo, is mainly known for its improvement in prostatic hiperplasia (BPH), urinary dysfunction and cytotoxic properties, also has also been used extensively as a hypoglycaemic agent. Many pharmacological studies have demonstrated hepatoprotection, inhibit benign prostatic hiperplasia, antioxidant, anticancer, antimicrobial, antiinflamatory, antidiabetic, and antiulcer activities supporting its traditional uses.

This paper describes the development and evaluation of a HPLC and UV spectrophotometric methods to quantify Cefaclor Monohydrate in Oral suspensions and Capsules. HPLC analysis were carried out using a C18 Knauer column and a mobile phase composed of Triethylamine:methanol:Acetonitrile:water (2:10:20:68) v/v%, with a flow rate of 1.0 mL/min and UV detection at 265 nm. For the spectrophotometric analysis, water was used as solvent and the wavelength of 264 nm was selected for the detection. Both methods were found to quantify Cefaclor monohydrate in Oral suspensions and Capsules accurately. Therefore HPLC and UV methods presented the most reliable results for the analyses of Oral suspension and Capsules.

Metabolic syndrome (MS) is defined by a cluster of interconnected factors that directlyincrease the risk of coronary heart disease (CHD), other forms of cardiovascularatherosclerotic diseases (CVD) and Type 2 diabetes mellitus (T2DM). Several studies have suggested important role of PPARδ in regulating lipid metabolism and energy homeostasis in muscle and fat. The present research work was undertaken to design and develop novel moieties derived from anthranilic acid scaffold as PPARδ agonists that can be developed further for the management of metabolic disorders. The molecules were designed using receptor based drug design approach, by utilizing the X-ray crystallographic information of PPARδ from PDB database. Based on the pharmacophoric requirements for PPARδ binding, the anthranilic acid nucleus was chosen for the design of newer analogs by substitution of amide linker and introduction of lipophilic groups on aromatic system by using sulphonamide group as a linker. Amongst the several synthesized anthranilic acid derivatives, 5-chloro-2- [3-(4-nitro-phenylsulfamoyl)-benzoyl amino]-benzoic acid showed highest antidiabetic activity. The experimental results were found to be in concordance with that of the in silico results. Overall, this research work revealed the potential of novel anthranilic acid based PPARδ agonists in the management of MS. Further, these molecules can serve as the starting point for the development of more potent lead molecules for MS.

Our previous work showed that in pancreatic INS-1 cells, geniposide exerted a contrary role on both glucosestimulated insulin secretion (GSIS) and glucose uptake and metabolism in the presence of low and high glucose. But the molecular mechanisms are presently not well understood. In the present study, we design to probe the role of AMP-activated protein kinase (AMPK) and NAD+- dependent deacetylase sirtuin-1 (SIRT1) on geniposide regulating GSIS, and analyze the interaction between AMPK and SIRT1 in pancreatic β cells. Our results indicate that geniposide induce the phosphorylation of AMPK and enhance the expression of SIRT1 in the presence of low concentration of glucose, but in the presence of high concentrations of glucose, geniposide played a contrary role on those. Furthermore, Compound C (an AMPK inhibitor) and Ex527 (a potent and selective inhibitor of SIRT1) prevent the effects of geniposide on glucose uptake, ATP production and GSIS in INS-1 cells. Taken together, our findings suggest that AMPK/SIRT1 are associated with the role of geniposide on energy balance in INS-1 cells.

In crystal structures, if each crystal cell is a special rectangular box (length × width × height=23 × 11.5 × 11.5 angstroms3), then how to pack these cells onto a enough hard base of a (46 × 46 angstroms2) square in order to make the crystal reach the stablest/optimal structure as high as the crystal it is? This is a practical problem that we are always thinking in our mind. This short article is to present an algorithm to solve this problem.

In this study, Cytochrome b (mitochondrion) protein has been used to investigate its role in antigenicity. Cytochrome b (mitochondrion) protein sequences (367 aa protein) is analyzed through different types B- cell epitope prediction methods. We found that the region of maximal hydrophilicity is likely to be an antigenic site, having hydrophobic characteristics, because the terminal regions of antigen protein is solvent accessible and unstructured, antibodies against those regions are also likely to recognize the native protein. It was seen that an antigen protein is hydrophobic in nature and contains segments of low complexity and high-predicted flexibility. The predicted antigenic protein segments of Cytochrome b (mitochondrion) can take active part in the host immune reactions. In this research, we have also used PSSM and SVM algorithms for the prediction of MHC class I and II binding peptide, antigenicity, Solvent accessibility, polar and nonpolar residue to analyse the regions that are likely exposed on the surface of proteins which are potentially antigenic that allows potential drug targets to identify active sites against infection as well as to design effective drug for treatment.

Acid-base titration of paracetamol in nonaqueous solvents was done. Procedure was followed for titration of paracetamol in different media like acetic acid, pyridine, dimethlformamide and ethyl alcohol with standard perchloric acid in glacial acetic acid, sodium ethoxide in ethyl alcohol using plantinum-calomel as well as glass-calomel electrode system. The equivalence point was located as accurately as possible by a differential graph of ΔE/ΔV or ΔpH/ΔV against V and concentration of test solution was computed. The acid-base titration of paracetamol is rapid and reproducible, and permits its determination in medicinal sample. The electrode systems vary with the solvent employed. The platinum-calomel electrode system is suitable where the solvent is glacial acetic acid in this case perchloric acid in glacial acetic acid is the titrant while the glass-calomel electrode system is suitable where the solvent is either pyridine, an alcohol or dimethyiformamide, the titrant consists of sodium ethoxide in ethyl alcohol.

The oxidation of the biologically very important dimethyl sulfoxide system has been the subject of investigations. In present study Dimethyl sulfoxide (DMSO) can be oxidized to dimethyl sulfone by anodic electrolysis at a rotating platinum electrode. The polarographic method has been used to study qualitatively the effect of maxima suppressor gelatin, fuchsin, methyl red, thymol blue and supporting electrolyte HCl, CH3COOH on oxidation wave of DMSO. Polarographic oxidation of DMSO in 0.1 M HCl, 0.1 M CH3COOH solution using optimum concentration of fuchsin, methyl red, thymol blue as surface active substances is followed to determine the DMSO present in synthetic sample by calibration method. Wave analysis indicate the irreversible nature of the oxidation process which involves oxidation of dimethyl sulfoxide to dimethyl sulfone thereby increasing the oxidation state of sulphur from +2 to +4 state.

Present paper deals with polarographic study of effect of maxima suppressors and supporting electrolytes on anodic waves of meta-hydroxyacetanilide and polarographic determination of meta-hydroxyacetanilide under optimum concentration of maxima suppressors and supporting electrolytes. The polarographic method has been developed to study qualitatively the effect of maxima suppressor (fuchsin) and supporting electrolyte (nitric acid) on oxidation wave of meta-hydroxyacetanilide. Polarograms of system were recorded between 500 to 1300 mV by using Rotating Platinum micro Electrode as anode and Saturated Calomel Electrode as cathode on D.C. Recording Polarograph using Omniscribe recorder. It shows a similar behavior to that observed for paracetamol. It produces anodic wave at rotating platinum electrode. The oxidation yields the 3-N-acetylaminosemiquinone and represents a reversible reaction. Polarographically a value of 900 mV is found for decomposition potential of meta-hydroxyacetanilide. Wave analysis point to 1-electron step for each wave. Waves of meta-hydroxyacetanilide are only proportional to concentration at low concentrations.

Benzo[h]naphtho[1,2-b][1,6]naphthyridine and its isomeric benzo[b]naphtho[1,2-h][1,6]naphthyridine with aliphatic, aromatic and hetero substitution were synthesized and screened for its antiproliferative activity against four human cancer cell lines. Among these, HeLa cells are more susceptible to compounds 3a, 3b, 9a and 9b with IC50 values of 3.62, 1.05, 6.21 and 1.41 μM respectively. Interestingly chloro substituted compound 9b showed IC50 values of 5.93, 7.01, and 6.81 μM against MCF7, K562 and Hep-G2 cancer cells, which is more active than the standard adriamycin. Furthermore chloro substituted compound 3b displayed good activity against MCF7 (IC50 6.63 μM) and K562 (IC50 7.23 μM) cancer cell lines. This study also revealed that, benzo[h]naphtho[1,2-b][1,6] naphthyridine series were more active than its isomeric benzo[b]naphtho[1,2-h][1,6] naphthyridines.