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Objective: The objective of the present study was to develop and validate a stability indicating RP-HPLC method for Lumefantrine (LF) and its organic impurities using a central composite design (CCD). Methods: A specific, simple quality control friendly isocratic elution method using reverse phase HPLC was developed for quantification of Lumefantrine (LF) and its organic impurities at a wavelength of 265 nm. The chromatographic separation was achieved on the column of Thermo Hypersil ODS C18 (150x4.6 mm, 3µ) with a buffer containing 0.1percent formic acid and acetonitrile 10:90 v/v as a mobile phase with a flow rate of 1.6 ml/min at 35 °C with a run time of 10 min. Based on the preliminary trials, CCD was employed to check the effect of independent variables such as Acetonitrile ratio (A), Flow rate (B), and Column oven temperature (C). While resolution between Lumefantrine (LF) and Impurity-A (X1), Impurity-A and Impurity-B (X2), and Plate count of Lumefantrine (LF) (X3) were considered as dependent variables and statistical evaluation performed by using design expert software. The optimized conditions were validated as per ICH guidelines. Results: The retention time of LF and its organic impurities were 1.9 min, 3.0, 4.5, and 6.4 min, respectively. Design space was established and desirability was found. LOD and LOQ for the Lumefantrine (LF) and its impurities were established with respect to test concentration. The plotted calibration curves were linear with a regression coefficient of R2>0.99, indicating that the linearity was within the limit. As a part of method validation, the parameters like Specificity with forced degradation, Linearity, Precision, Accuracy, Ruggedness, and Robustness were determined and the results were found to be within the allowable limits. Conclusion: The method developed and validated was found to be suitable for routine analysis and to be used for the measurement of Lumefantrine and its impurities. Since there is no stability indicating the RP-HPLC method with design space was reported in the literature, there is a need to develop quantitative methods under different conditions to achieve improvement in specificity and selectivity.

1,3,4-Oxadiazole is a five membered heterocyclic nucleus and a versatile lead structure, where its derivatives showed broad and potent biological functions especially as anticancer and antiviral agents which are associated with various mechanisms such as inhibition of different enzymes, kinases and growth factors. The present review summarizes various synthetic procedures and highlights the targeted inhibitory activities of 1,3,4-oxadiazoles as potential anticancer and antiviral agents along with their structure activity relationship. Molecular modeling and pharmacokinetic studies on 1,3,4-oxadiazoles proved a change in their polarity, flexibility and metabolic stability led to their improved biological activity potential. Among all the substituted 1,3,4-oxadiazoles, the mono- and 2,5-disubstituted derivatives showed considerable biological activities especially as anticancer and antiviral agents. Hence, scientists/researchers considered these as future lead molecules to treat cancer and viral infections along with other diseases. In future, the oxadiazole motif is likely to be incorporated in various other therapeutic molecules.

Twenty novel pyrimidine derivatives were synthesized from 2,5-dichloro-3-acetylthienyl chalcones by reacting with guanidine HCl in presence of KOH and ethanol under reflux for 6 h. Their structural characterizations were evaluated by ATR-FTIR, 1H NMR, 13C NMR, mass spectroscopy. They were also screened for antifungal, antitubercular and cytotoxicity activities. They were displayed good antifungal activity (MIC = 32-125 μg/mL) against Aspergillus niger and Candida tropicalis fungal species except compound 15 with 4"-pyridinyl moiety (MIC = 8.00 μg/mL) being more potent. Compound 5 with 2",4"-dichlorophenyl moiety was shown with good antitubercular activity (MIC = 6.2 μg/mL) against Mycobacterium tuberculosis H37Rv (MTB) stain. They have also tested for in vitro cytotoxicity activity against DU-145 prostate cancer cell lines. In which the compound 15 with 4"-pyridinyl moiety (IC50 = 2.0 ± 0.1 μg/mL) and compound 17 with 2"-pyrrolyl moiety (IC50 = 6.0 ± 0.1 μg/mL) possess highly potent antiprostate cancer properties. The molecular docking was done with the crystalline structure of mitochondrial 2-enoyl thioester reductase Etr1p/Etr2p heterodimer from Candida tropicalis fungal species with compound 15 (-7.80 kcal/mol) and shown greater binding affinity than fluconazole (-7.60 kcal/mol). Docking was performed with protein crystalline structure (PDB ID: 2WEE) of Mycobacterium tuberculosis H37Rv (MTB) stain and among all, compound 5 was exhibited good binding affinity (-6.90 kcal/mol), compared to pyrazinamide (-4.10 kcal/mol). The protein crystalline structure of a mutant androgen receptor (AR) ligand-binding domain (LBD) (PDB file: 1GS4) was tested with compounds 15 and 17 (-7.60 and -8.20 kcal/mol). They were exhibited good binding properties compared to methotrexate (-5.10 kcal/mol). Hence, these novel pyrimidine compounds are as lead compounds as antifungal, antitubercular and cytotoxic agents.

Prof. Venkata Rao born on 1st July, 1931 completed his studies in Andhra University during the years 1950- 59. He was one of the founder members of the Department of Pharmaceutical Sciences at Andhra University, Visakhapatnam and instrumental in the growth of institution by way of his rich contributions over a period of 4 decades in different capacities from 1953-91. He visited UK on a Commonwealth Scholarship and worked under Prof. Sir James Baddiley FRS, in Newcastle University, which led to the award of a Ph. D. degree in Bio-Organic Chemistry in 1964 on the topic "Studies on the Capsular Polysaccharides of Pneumococcus Type 10A", which work won him K. N. Welch Memorial Prize and this work also formed part of the 23-valent Pneumococcal vaccine (Pneumovax-23rm), which is official to Indian pharmacopeia 2007. Earlier to this significant contribution, Prof. Venkata Rao’s D. Sc. work at Andhra University on Thevetia neriifolia resulted in the discovery of a new clinically useful cardiotonic glycoside, peruvoside, the first modern drug discovery in India acclaimed by the International Scientific Community. This drug was developed for therapeutic use by M/s E. Merck and manufactured by an Italian Pharma Company, Simes, was listed in the Merck Index and Martindale-The Extra Pharmacopeia. Several other compounds his group isolated and worked on have found a place in the Merck Index.

The present study aims to evaluate antistress and neuropharmacological parameters of ethanolic, ethyl acetate and hexane flower extracts of Tecoma gaudichaudi. Forced swim stress was used to evaluate antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. In the present study, the extracts (200 and 400 mg/kg, p.o.) were investigated for nootropic activity in rats with and without stress. Cook’s pole climbing apparatus measures conditioned avoidance response, elevated plus maze determines transfer latency and staircase test calculates the number of steps climbed and rearings in normal and stress induced rats to assess cognitive-improving activities. Cognition was enhanced by daily administration of Tecoma gaudichaudi extracts at doses of 200 and 400 mg/kg, p.o. in dose dependent manner in normal rats. Tecomine and its derivatives were isolated from alkaloidal fraction.

Infectious diseases are one of the common problems encountered globally. Even though there are a number of drugs available in the market for the treatment of infectious diseases, still many new molecules are required due to the problems with the existing drugs. Hence we prepared a series of chalcones (A1-A10) containing nitrophenyl moieties by Claisen-Schmidt condensation reaction. All the ten compounds were characterized by IR, NMR, Mass spectroscopy and elemental analysis. The compounds were further screened for antitubercular activity employing MABA assay and antibacterial and antifungal activities by cup plate method against selected tubercular, bacterial and fungal organisms. The compound A9 displayed potent antitubercular activity with MIC 11.02±0.030, whereas the compound A3 showed superior antibacterial and antifungal activities. Further, molecular docking studies were performed on Thymidine Kinase (TMP) of Mycobacterium tuberculosis by employing AU autodocker. The docking scores were in association with the in vitro MABA results and also identified the potent nature of A9 with the docking score -6.7. This study helped to identify novel nitrophenyl derivatives against thymidylate kinase.

Background: Many synthetic procedures were reported till date to prepare pyrazoline derivatives. Some have published pyrazolines from different chalcone derivatives in the literature. Objective: A series of new pyrazolines containing novel 2,5-dichloro-3-acetylthiophene chalcone moiety (PZT1-PZT20) have been synthesized, characterized by 1HNMR and 13CNMR and evaluated for them in vitro antitubercular activity against M. tuberculosis H37Rv strain and in vitro anticancer activity against DU-145 prostate cancer cell lines and all compounds were also screened for molecular docking studies against specific targeted protein domains. Methods: All compounds were screened for potential activity against Mycobacterium tuberculosis H37Rv (MTB) strain and anticancer activity against DU-149 prostate cancer cell lines using MTT cytotoxicity assay. Results: Among the series, compound PZT5 with 2”, 4”-dichlorophenyl group at 5-position on the pyrazoline ring exhibited the most potent antitubercular activity (MIC=1.60 µg/mL) and compounds PZT2, PZT9, PZT11, PZT15, and PZT20 showed similar antitubercular activity against standard pyrazinamide (MIC=3.12 µg/mL) by broth dilution assay. PZT15 and PZT17 with 4”- pyridinyl and 2”-pyrrolyl groups on pyrazoline ring were found to exhibit better anticancer activity against DU-149 prostate cancer cell lines with IC50 values of 2.0±0.2 µg/mL and 6.0±0.3 µg/mL respectively by MTT assay. The preliminary structure-activity relationship has been summarized. The molecular docking studies with crystalline structures of enoyl acyl carrier protein reductase InhA interaction with target protein (2NSD; PDB and 3FNG; PDB) of Mycobacterium tuberculosis H37Rv (MTB) strain have also exhibited good ligand interaction and binding affinity. Ligand interaction and binding affinity were estimated using crystal structures of both types of enoyl acyl carrier protein reductase InhA (3FNG.pdb) and found to be much higher (-16.70 to - 19.20 kcal/mol) compared with pyrazinamide (-10.70 kcal/mol) as a standard target molecule. Whereas the binding affinities of six active compounds with crystal structure of other type of enoyl acyl carrier protein reductase InhA (2NSD.pdb) were much similar and higher (-9.30 to - 11.20 kcal/mole) than pyrazinamide (-11.10 kcal/mole). Conclusion: These new pyrazolines would be promising potent inhibitors of drug sensitive and drug resistant Mycobacterium tuberculosis strain and potential anticancer agents against prostate cancer and other prototypes of cancers.

According to WHO, cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Among several factors involved in the pathogenesis of cancer, free radical formation followed by damage to DNA and cell protein is one of the causes. Natural plant products have gained enormous interest in the prevention or treatment of chronic diseases. Ferulic acid, like other phenolic acids (caffeic acid, sinapic acid) possess anti cancer activity. A series of ferulic esters (FE1 - FE11) and ferulic amides (FA1 - FA10) were synthesized and evaluated for their cytotoxic activity.

We have earlier reported the synthesis of the three major curcuminoids of turmeric employing a new strategy involving the use of borontrifluoride instead of boric oxide to protect the active methylene group of acetylacetone in reaction with aromatic aldehydes. We have now synthesized monomethyl products of curcumin and demethoxycurcumin by the same route and characterized them through their physical, chemical and spectral properties. As expected, a single monomethylcurcumin was obtained whereas we got two isomeric, monomethyl demethoxycurcumins when appropriate aromatic aldehydes were used in the condensation reaction. All the compounds were characterized through their difluoroboronites. The isomeric monomethyldemethoxycurcumins, reported for the first time, are distinctly different in melting point, thin layer chromatography and high performance liquid chromatography while their difluorobornites differed in ultra violet spectra. Dimethyl-bis-demethoxycurcumin and its difluoroboronite were prepared for the first time to confirm the involvement of 4/4’-hydroxyl in curcuminoids in quinonoid formation and consequent stability of their difluoroboronites. The monomethylcurcuminoids, especially those of demethoxycurcumin would be of interest for biological activity studies in comparison with curcumin.

Background: A simple, sensitive, linear, precise, and accurate method by gradient reversed-phase-high performance liquid chromatography for the simultaneous estimation of metformin (MET), voglibose (VOG) and glimepiride (GLI) in bulk and in their combined tablet dosage form was developed and validated. Materials and Methods: The separation of the three drugs was based on the use of Inertsil ODS 3V (150 × 4.6 mm, i.e. 5 μm) column in a gradient mode. Mobile phase consisted of 0.02 M Phosphate buffer adjusted to pH 2.5 using dilute orthophosphoric acid (solvent A) and acetonitrile (solvent B) was set with gradient programming for 18 min and was delivered at 1 ml/min fl ow rate and effl uents are achieved with variable wavelength: Photodiode array detector at 230 nm. Results: The retention times of MET, VOG, and GLI were found to be 2.423, 8.191, and 11.708, respectively. The percentage assay of MET, VOG, and GLI was found to be 99.92%, 99.32, and 99.72%, respectively. Calibration curves were linear for MET, VOG and GLI at concentration ranges of 200-600 μg/ml, 0.08-0.24 μg/ml, and 0.8-2.4 μg/ml with the regression coeffi cient of 0.999 for all the three drugs and precise with (% relative standard deviation Conclusion: The method was validated by determining its linearity, accuracy, precision, system suitability and can be employed for routine quality control analysis as per International Conference on Harmonization guidelines. Key words: Glimepiride, gradient reversed-phase-high performance liquid chromatography, International Conference on Harmonization guidelines, metformin, validation, voglibose.

A series of novel sulfonyl derivatives 3-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-4-phenyl-4H-1,2,4-triazoles 4a–4e, isopropyl thiazole-derived schiff bases 8a–8l, and 2-(substituted benzylsulfonyl)-5-(4-isopropylthiazol-2-yl)-1,3,4-oxadiazoles 11a–11e were synthesized and characterized by IR, 1H NMR, 13C NMR, elemental, and mass spectral analysis. All the compounds exhibited moderate to significant antibacterial and antifungal activities. Results of the antitubercular screening against Mycobacterium tuberculosis H37Rv ascertain compounds 4e, 8b, and 8f as excellent antitubercular molecules, when compared with first line drug isoniazid (0.25 μg/mL).

A focused library of 4,5-dihydropyrazole dervivatives (4, 5, 6, 7a–h, 8, 9a–g, and 10a–g) were synthesized from novel 5-(2,6-difluorophenyl)-3-phenyl-4,5-dihydropyrazole-1-carbothioamide 4. The synthesized compounds were characterized using elemental analysis and spectral data (IR, mass spectra, 1H and 13C NMR) and evaluated for antimicrobial activity by broth dilution method and in vitro anticancer activity. Among the synthesized compounds 7a, 9c, 9g, and 10d exhibit broad spectrum antimicrobial activity against tested microbial strains. The in vitro cancer results ascertain 7a, 9c, and 10d are most potent molecules in comparison to reference standard cisplatin.

Chalcones afford a facile route of access to many of the heterocyclic systems containing oxygen and nitrogen. An attempt is therefore made to synthesize chalcones from 3-acetylpyridine by reaction with either aromatic or heteroaromatic aldehyde using Claisen-Schmidt condensation. The resulting chalcones after purification and characterization by physical and spectral methods have been successfully converted into substituted pyrimidines by reaction with guanidine hydrochloride. All these compounds were characterized by means of their IR, 1 H NMR, 13 C NMR and mass spectral data.

A series of novel 4-isopropylthiazol-4-phenyl-1,2,4-triazol derivatives, N′-(substituted benzylidene)-2-(5-(4-isopropylthiazol-2-yl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)acetohydrazides 4a–e, 4-isopropylthiazol-2-yl-4′-phenyl-4′H-1′, 2′,4′-triazol-3′-ylthio (substituted methyl benzylidene) acetohydrazides 5a–f, 3-(4-isopropylthiazol-2-yl)-4-phenyl-5-(5-substituted-1,3,4-oxadiazol-2-ylthio)-4H-1,2,4-triazole derivatives 6a–f and N-acetyl-5′-(4-isopropylthiazol-2-yl)-4′-phenyl-4′H-1,2,4-triazol-3′-ylthio) acetohydrazide 7 were synthesized and characterized by spectroscopy, elemental, and mass spectral analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal, and antitubercular activity against Mycobacterium tuberculosis (M. tuberculosis) H37Rv strain by broth dilution assay method. All the compounds exhibited moderate to significant antibacterial and antifungal activities. Results of the antitubercular screening against Mycobacterium tuberculosis H37Rv showed that compounds 4c and 6c exhibited good antitubercular activity when compared with first line drug isoniazid.

A series of novel dibenzo[b,d]furan mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit Protein Tyrosine Phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Structure–activity relationship study led to the identification of potent compound 5E which inhibited PTP1B with IC50 value of 82 ± 0.43 nM. Compound 5E was screened in vivo as drug candidate for anti-diabetic activity using rosiglitazone maleate as the standard. Compound 5E showed significant reduction in body weight, fed-state whole blood glucose (WBG), fasting WBG, plasma glucose and plasma cholesterol levels and non-significant reduction in fasting plasma triglyceride levels in ob/ob mice.

QSAR analysis on a set of synthesized chalcone derivatives tested for growth inhibitory activity against Bacillus pumilis was performed by using multiple regression procedure. The activity contributions of these compounds were determined from regression equation and the validation procedures to analyze the predictive ability of QSAR model were described. The generated model from a 25 molecule training set and 7 molecule validation set using 47 independent variables revealed that an increase in ADME Weight, Kappa2 index and a decrease in HOMO energy as favorable descriptors for Bacillus pumilis inhibition.

In an effort to develop antimicrobial agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehydes in the presence of aqueous solution of potassium hydroxide and ethanol at room temperature. The synthesized compounds were characterized by means of their IR,1H-NMR spectral data and elemental analysis. All the compounds were tested for their antibacterial and antifungal activities by the cup plate method.

A series of novel isochroman mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Analysis of structure-activity relationships led to the identification of potent compound 4n which inhibited PTP1B with IC(50) value of 51.63+/-0.91 nM. In general, high potency was associated with a dithiolane ring with a spacer of five carbons to the isochroman ring. Compound 4n has been selected for in vivo evaluation as drug candidate for anti-diabetic activity.

A series of novel isochroman mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Analysis of structure-activity relationships led to the identification of potent compound 4n which inhibited PTP1B with IC(50) value of 51.63+/-0.91 nM. In general, high potency was associated with a dithiolane ring with a spacer of five carbons to the isochroman ring. Compound 4n has been selected for in vivo evaluation as drug candidate for anti-diabetic activity.

Five novel chalcones were synthesised by condensing 2-hydroxy-1-acetonaphthone with aldehyde derivatives in dilute ethanolic potassium hydroxide solution at room temperature according to Claisen-Schmidt condensation and another five novel chalcones were prepared by refluxing 3-acetyl coumarin with aldehydes in the presence of piperidine in ethanol. All these compounds were characterised by means of their IR,1H NMR spectroscopic data and microanalyses. The antimicrobial activity of these compounds were evaluated by the cup plate method.

Five new 1,3,5-triphenyl-2-pyrazolines were synthesised by reacting 1,3-diphenyl-2-propene-1-one with phenyl hydrazine hydrochloride and another five new 3-(2''-hydroxy naphthalen-1''-yl)-1,5-diphenyl-2-pyrazolines were synthesised by reacting 1-(2'-hydroxynaphthyl)-3-phenyl-2-propene-1-one with phenyl hydrazine hydrochloride. The structures of the compounds were proved by means of their IR, (1)H NMR spectroscopic data, and microanalyses. The antidepressant activity of these compounds was evaluated by the 'Porsolt behavioural despair test' on Swiss-Webster mice.1-Phenyl-3-(2''-hydroxyphenyl)-5-(4'-dimethylaminophenyl)-2-pyrazoline, 5-(4'-dimethylaminophenyl)-1,3-diphenyl-2-pyrazoline, 1-phenyl-3-(2''-hydroxynaphthalen-1''-yl)-5-(3',4',5'-trimethoxyphenyl)-2-pyrazoline, 1-phenyl-3-(4''-methylphenyl)-5-(4'-dimethylaminophenyl)-2-pyrazoline and 1-phenyl-3-(4''-bromophenyl)-5-(4'-dimethyl amino phenyl)-2-pyrazoline reduced immobility times 25.63-59.25% at 100mg/kg dose level. In addition, it was found that the compounds possessing electron-releasing groups such as dimethyl amino, methoxy and hydroxyl substituents, on both the aromatic rings at positions 3 and 5 of pyrazolines, considerably enhanced the antidepressant activity when compared to the pyrazolines having no substituents on the phenyl rings.

A new isoflavone, characterized as 7,8-methylenedioxy-4'-methoxyisoflavone by chemical and spectral studies, has been isolated from the whole plant of Indigofera linnaei.

Chemical examination of the chloroform extract of the roots of Milletia auriculata has yielded three new prenylated isoflavones in addition to the previously reported isoflavones isoauriculatin, auriculin, millettin, auriculatin, scandenone and the rotenoid sumatrol.

A new flavanone, maxima flavanone A, was isolated from the chloroform extract of the roots of Tephrosia maxima along with maxima isoflavone J and t

Chemical examination of the petroleum and chloroform extracts of the roots of Tephrosia spinosa has yielded two new chalcones, spinochalcones A and B, in addition to the known chalcone flemistrictin A.