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In this study, twenty eight novel oxadiazole derivatives (5-32) of the marketed available non-steroidal anti-inflammatory drug (NSAID), ( S )-flurbiprofen (1), were synthesized via I 2 mediated cyclo-addition reaction in better yields. The synthesized hydrazone-Schiff bases were cyclized with iodine by using potassium hydroxide as a base in DMSO solvent to obtain oxadiazole derivatives (5-32). Structures of the synthesized products were confirmed with HR-ESI-MS, 1 H-NMR spectroscopy and CHN analysis. After structure confirmations all analogs were evaluated for urease ( in vitro ) inhibitory activity. Amongst the series, fourteen compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 were found to be excellent inhibitors of urease enzyme, having IC 50 values of 12 ± 0.9 to 20 ± 0.5 μM, better than the standard thiourea (IC 50 = 22 ± 2.2 μM), whereas the remaining fourteen derivatives displayed good to moderate activity. The in silico study was executed to analyse the interaction between the active site of the enzyme (urease) and the produced compounds. The docking study revealed that compounds 20, 26, 30, 24, 21, 16, 28, 31, 32, 7, 19, 13, 10, and 6 had lower docking scores than the standard compound thiourea and revealed better interactions with the urease enzyme., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Urease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis -Schiff base derivatives of benzyl phenyl ketone nucleus., Objective: Synthesis of benzyl phenyl ketone based bis -Schiff bases in search of potent urease inhibitors., Method: In the current work, bis -Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis -Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and 1 H NMR spectroscopy were used to clarify the structures of the created bis -Schiff base derivatives., Results: The prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives ( 3 - 9 ) showed excellent to less inhibitory activity when compared with standard thiourea (IC 50  = 21.15 ± 0.32 µM). Compounds 3 (IC 50  = 22.21 ± 0.42 µM), 4 (IC 50  = 26.11 ± 0.22 µM) and 6 (IC 50  = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC 50 value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC 50 values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Glioblastoma multiforme (GBM) is the most common and primary brain tumor with poor prognosis. They are removed by following tedious and life threatening surgeries. GBM stem cells (GSCs) are the main source of tumor recurrence after surgery. Hence, drugs are designed to overcome the recurrent glioblastoma malignant cells. Currently used chemotherapies are not cost effective as well as bear resistance. New and effective chemotherapeutic compounds are developed to overcome the intrinsic and acquired resistance. Dicoumarol derivative 3,3'-[(4-methoxyphenyl)methanediyl]bis(4-hydroxy-2Hchromen-2-one) (HL) and its triethylammonium salt triethylammonium3-[(4-methoxyphenyl)(4-hydroxy-2-oxo-2H-chromen-3-yl)methyl]-2-oxo-2H-chromen-4-olate (L) were synthesized and characterized using spectral and analytical techniques. The deprotonated compound L was further studied structurally using single crystal analysis. Cytotoxic studies against human glioblastoma cells A172 and LN229 were investigated both dose and time dependently and compared with the cytotoxicity of normal human astrocytes (NHA). The IC 50 value of HL against A172 was found to be lying within the range 2.68-0.95 μM whereas against LN229 the range was found to be 9.55-0.85 μM. Similarly, the compound L revealed range of 1.9-0.271 μM against A172 and 1.2-0.27 μM against LN229. Cell cycle arrest was observed in GBM cells treated with L compared to the control group, which suggested that L may trigger apoptosis in GBM cells according to cytotoxicity and flow cytometry results. The antioxidant activity of synthesized compounds was also investigated using DPPH free radicals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Dihydropyrazole (1-22) derivatives were synthesized from already synthesized chalcones. The structures of all of the synthesized compounds were confirmed by elemental analysis and various spectroscopic techniques. Furthermore, the synthesized compounds were screened against α amylase as well as investigated for antioxidant activities. The synthesized compounds demonstrate good to excellent antioxidant activities with IC 50 values ranging between 30.03 and 913.58 μM. Among the 22 evaluated compounds, 11 compounds exhibit excellent activity relative to the standard ascorbic acid IC 50 = 287.30 μM. Interestingly, all of the evaluated compounds show good to excellent α amylase activity with IC 50 values lying in the range between 0.5509 and 810.73 μM as compared to the standard acarbose IC 50 = 73.12 μM. Among the investigated compounds, five compounds demonstrate better activity compared to the standard. In order to investigate the binding interactions of the evaluated compounds with amylase protein, molecular docking studies were conducted, which show an excellent docking score as compared to the standard. Furthermore, the physiochemical properties, drug likeness, and ADMET were investigated, and it was found that none of the compounds violate Lipiniski's rule of five, which shows that this class of compounds has enough potential to be used as a drug candidate in the near future., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Antibiotic resistance is tricky enemy that challenges our healthcare system. It is a stealthy, adaptive and ever evolving opponent, which can take years to develop but can spread like wildfire. In this study, derivatives of chiral phthalimides were developed with this aim to control the growth of resistant strains of Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa by targeting their resistance causing proteins and explore their binding interaction focal points through computational docking. Total 8 novel chiral phthalimides were synthesized and its antibiogram analysis was done on Muller-Hinton Agar by disc diffusion method. Cytotoxicity studies were made to check efficacy of tested compounds on human RBCs and monitor release of hemoglobin absorbance at 540nm. By using in silico molecular approach, crystal structure of target protein was retrieved from Protein Data Bank and docked through Autodock vina and PyRx. The obtained results revealed that seven out of eight compounds have active inhibitory effects against virulent strains. Minimum Inhibitory Concentration (MIC) was measured for most potent compounds i.e., 2-(1,3-dioxoisoindolin-2-yl)-3-(4-hydroxyphenyl) propanoic acid (compound 7) and 3-(1,3-dioxoisoindolin-2-yl) propanoic acid (compound 8). Docking studies displayed a report of highest affinity binding points i.e., amino acids LYS315, ALA318, TYR150, THR262, HIS314 and ARG148 for compound 7 while ALA 318, LYS 315, ARG14 and ILE291 for compound 8.

The current research reports the synthesis of 14 para-substituted thiosemicarbazone derivatives in good to excellent yields using standard procedures. Initially, 4-ethoxybenzaldehyde ( 1 ) and 4-nitrobenzaldehyde ( 2 ) were refluxed with thiosemicarbazide in the presence of acetic acid in ethanol for 4-5 h. Then, various substituted phenacyl bromides were treated with the desired thiosemicarbazones ( 3 and 4 ) in the presence of triethylamine in ethanol with constant stirring for 5-6 h. The resulting derivatives were confirmed through electron impact mass spectrometry and 1 H NMR spectroscopy and evaluated for anticholinesterase inhibitory activity. Among the series, four compounds, 19 , 17 , 7 , and 6 , showed potent inhibitory activity against the acetylcholinesterase (AChE) enzyme, having IC 50 values of 110.19 ± 2.32, 114.57 ± 0.15, 140.52 ± 0.11, and 160.04 ± 0.02 μM, respectively, compared with standard galantamine (IC 50 = 104.5 ± 1.20 μM). Similarly, compounds 19 (IC 50 = 145.11 ± 1.03 μM), 9 (IC 50 = 147.20 ± 0.09 μM), 17 (IC 50 = 150.36 ± 0.18 μM), and 6 (IC 50 = 190.21 ± 0.13 μM) were the most excellent inhibitors of butyrylcholinesterase (BChE) when compared with the standard drug galantamine (IC 50 = 156.8 ± 1.50 μM). In silico studies were accomplished on the produced derivatives in order to explain the binding interface of compounds with the active sites of AChE and BChE enzymes., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In the present study, 28 acyl hydrazones ( 4-31 ) of flurbiprofen were synthesized in good to excellent yield by reacting different aromatic aldehydes with the commercially available drug flurbiprofen. The compounds were deduced with the help of different spectroscopic techniques like 1 H-NMR and HREI-MS and finally evaluated for in vitro urease inhibitory activity. All of the synthesized products demonstrated good inhibitory activities in the range of IC 50 = 18.92 ± 0.61 to 90.75 ± 7.71 μM as compared to standard thiourea (IC 50 = 21.14 ± 0.42 μM). Compound 30 was found to be the most active among the series better than the standard thiourea. A structure-activity relationship (SAR) study revealed that the presence of electron-donating groups on the phenyl ring plays a prominent role in the inhibition of the urease enzyme. Moreover, in silico molecular modeling analysis was carried out to study the effect of substituents in synthesized derivatives on the binding interactions with the urease enzyme., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Polyhydroquinoline (PHQ) are the unsymmetrical Hantzsch derivatives of 1,4-dihydropyridines with several biological applications. In this work, twenty-five ( 3 - 27 ) new Schiff's base derivatives of polyhydroquinoline hydrazide were synthesized in excellent to good yields by a multi-component reaction. The structures of the synthesized products ( 1 - 27 ) were deduced with the help of spectroscopic techniques, such as 1 H-, 13 C -NMR, and HR-ESI-MS. The synthesized products ( 1 - 27 ) were tested for their antibacterial and in vitro calcium -channel-blocking (CCB) potentials using the agar-well diffusion method, and isolated rat aortic ring preparations, respectively. Among the series, sixteen compounds were found to inhibit the growth of Escherichia coli and Enterococcus faecalis . Among them, compound 17 was observed to be the most potent one at a dose 2 µg/mL, with an 18 mm zone of inhibition against both bacteria when it was compared with the standard drug amoxicillin. Eight compounds showed CCB activity of variable potency; in particular, compound 27 was more potent, with an EC 50 value of 0.7 (0.3-1.1) µg/mL, indicating their CCB effect.

Background: Hydrazides play a vital role in making biologically active compounds in various fields of chemistry. These determine antioxidant, antidepressant, antimalarial, anti-inflammatory, antiglycating, and antimicrobial activity. In the present study, twenty-three new N' benzylidene-4-(tert-butyl)benzohydrazide derivatives ( 4 - 26 ) were synthesized by the condensation of aromatic aldehydes and commercially available 4-(tert-butyl)benzoic acid. All the target compounds were successfully synthesized from good to excellent yield; all synthesized derivatives were characterized via spectroscopic techniques such as HREI-MS and 1 H-NMR. Synthesized compounds were evaluated for in vitro urease inhibition. All synthesized derivatives demonstrated good inhibitory activities in the range of IC 50 = 13.33 ± 0.58-251.74 ± 6.82 µM as compared with standard thiourea having IC 50 = 21.14 ± 0.425 µM. Two compounds, 6 and 25 , were found to be more active than standard. SAR revealed that electron donating groups in phenyl ring have more influence on enzyme inhibition. However, to gain insight into the participation of different substituents in synthesized derivatives on the binding interactions with urease enzyme, in silico (computer simulation) molecular modeling analysis was carried out.

Background: Extra pulmonary tuberculosis (EPTB) constitutes 18% of all tuberculosis (TB) cases and tuberculous lymphadenitis (TBL) constitutes 20-40% of EPTB. Diagnosis of TBL is challenging because of the paucibacillary nature of the disease., Objective: To investigate the diagnostic potential of a new antigen detection test based on the detection of M. tuberculosis complex specific antigen MPT64 from fine needle aspirate (FNA) cytology smears and biopsies obtained from patients with clinically suspected TBL using immunohistochemistry (IHC)., Materials and Methods: This study was conducted at Khyber Teaching Hospital and Rehman Medical Institute, Peshawar, Pakistan, from January 2018 to April 2019. Samples, including FNA (n = 100) and biopsies (n = 8), were collected from 100 patients with presumptive TBL. Direct smears and cell blocks were prepared from the FNA samples. All samples were subjected to hematoxylin-eosin (H&E) staining, Ziehl-Neelsen (ZN) staining, and immunostaining with polyclonal anti-MPT64 antibody. The culture was performed only for biopsy specimens. All patients were followed until the completion of anti-TB treatment. The response to treatment was included in the composite reference standard (CRS) and used as the gold standard to validate the diagnostic tests., Results: The sensitivity, specificity, positive and negative predictive values for ZN staining were 4.4%,100%,100%,56%, for culture were 66%,100%,100%,50%, for cytomorphology were 100%,90.91%,90%,100%, and for immunostaining with anti-MPT64 were all 100%,respectively. The morphology and performance of immunohistochemistry were better with cell blocks than with smears., Conclusion: MPT64 antigen detection test performed better than ZN and cytomorphology in diagnosing TBL. This test applied to cell blocks from FNA is robust, simple, and relatively rapid, and improves the diagnosis of TBL., Competing Interests: The authors have declared that no competing interests exist.

Polymer based nanoparticles for drug delivery is an alternative approach to overcome drug resistance and drug toxicity especially for cutaneous leishmaniasis treatment. The present study shows synthesis and characterization of Miltefosine loaded chitosan nanoparticles (MFS-CNPs). The synthesized MFS-CNPs were experimented to evaluate the in vitro cytotoxicity and efficacy of the synthesized drug loaded nanoparticles by hemolysis assay and 3-(4, 5- dimethylthiazol-2-yl)-2,5-diphenyletetrazolium bromide (MTT) assay. MFS-CNPs were synthesized by ionic gelation method with sodium tripolyphosphate. The characterization of synthesized NPs was performed to observe the surface morphology, encapsulation efficacy, drug loading content, average size, and zeta potential. In vitro MTT assay was performed to calculate half maximal inhibitory concentration value of synthesized nanoparticles against promastigotes and axenic amastigotes of L. tropica . By using Scanning electron microscope, MFS-CNPs displayed spherical shape having a mean size of 70 nm along with high EE (97%), DLC (91%) and negative surface charge (- 28.0 mV). Dynamic light scattering shows the average size of NPs was 91.4 nm. Moreover, less than 5% hemolytic activity was observed in MFS-CNPs as compared to free MFS in different concentrations (100 μg/ml, 125 μg/ml, 150 μg/ml).It was observed that the effect of MFS-CNPs and free MFS on both forms of the parasite was dose and time dependent. However, the cytotoxic effects of MFS-CNPs were more salient than free MFS on both forms of L. tropica . Using MTT assay, free MFS presented low efficacy at higher concentrations (30 µg/ml) with 21.4 ± 1.3 and 20.5 ± 1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 h incubation. While MFS-CNPs showed strong antileishmanial effects on both forms of L. tropica (11 ± 0.3 and 14 ± 0.8) mean viability rate after 72 h incubation at (30 µg/ml). When analyzed statistically by the software, Graph Pad Prism version 5, the IC50 value of MFS-CNPs (0.0218 ± 0.01 µg/ml) against promastigotes was effective than free MFS (0.3548 ± 0.17 µg/ml). Similarly, MFS-CNPs activity against axenic amastigotes (0.1008 ± 0.02 µg/ml) was potent than free MFS (0.5320 ± 0.21 µg/ml). Hence, MFS-CNPs exhibited significant antileishmanial activity in vitro. In conclusion, MFS-CNPs manifested enhanced in vitro Leishmanicidal and less hemolytic activity; however more studies are needed to support its efficacy in both animal and human cutaneous leishmaniasis., Competing Interests: Conflict of interestWe have no conflict of interest to disclose regarding this manuscript. As a corresponding author, I confirm that the manuscript has been read and approved for submission by all the named authors., (© Indian Society for Parasitology 2021.)

Aims: To synthesize bis-1,3,4-oxadiazole derivatives as novel and potential urease inhibitors., Background: Despite many important biological activities associated with oxadiazoles, they are still neglected by medicinal chemists for their possible urease inhibitory activity. Keeping in view the countless importance of urease inhibitors, we have synthesized a new library of substituted bisoxadiazole derivatives (1-21) to evaluate their urease inhibitory potential., Objective: The aim includes the synthesis of substituted bis-oxadiazole derivatives (1-21) in order to evaluate their urease inhibitory potential., Methods: Bis-1,3,4-oxadiazole derivatives 1-21 were synthesized through sequential reactions using starting material isophthalic acid. Esterification reaction was done by refluxing in methanol for 2 h in the presence of the catalytic amount of concentrated H 2 SO 4 till dissolution. In the second step, dimethyl isophthalate and hydrazine hydrate in excess (1:5) were refluxed in methanol to afford isophthalic dihydrazide. Then, isophthalic dihydrazide was treated with different substituted benzaldehydes in a 1:2 ratio under acidic conditions., Results: In vitro urease, the inhibitory activity of the synthesized compounds was evaluated and the results demonstrated good activities with IC 50 values in the range of 13.46 ± 0.34 to 74.45 ± 3.81 μM as compared to the standard thiourea (IC 50 = 21.13 ± 0.415 μM). Most of the compounds were found to be more potent than the standard. The structure-activity relationship (SAR) suggested that the variations in the inhibitory activities of the compounds were due to different substitutions. Furthermore; in silico study was also performed., Conclusion: Current study identified a new class of urease inhibitors. All synthetic compounds 1-21 showed potent as well as good to moderate urease inhibitory activities except 3. SAR suggested that hydroxy-bearing analogs were identified exceptionally well. Molecular docking revealed many important interactions made by compounds with the active site of the urease enzyme., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cutaneous leishmaniasis being a neglected tropical disease (NTD) faces several challenges in chemotherapy. If infected with secondary bacterial infections, the treatment regime of cutaneous ulcers in cutaneous leishmaniasis is further complicated which usually require two or more than two chemotherapeutic agents for healing. In the current study, seven curcumin-loaded self-emulsifying drug delivery system (cu-SEDDS) formulations (namely F1-F7) were prepared by mixing different excipients (oils, surfactants, and co-solvents) through stirring (vortex) and sonication. The formulations were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential by zeta sizer. The cu-SEDDS formulations displayed different sizes ranging from 32.4 up to 80.0 nm. The zeta potential of the formulations ranged from - 1.56 up to - 4.8. The antileishmanial activities of the cu-SEDDS formulations in terms of IC 50 against Leishmania tropica ranged from 0.19 up to 0.37 μg/ml. The minimum inhibitory concentrations (MICs) of these formulations against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae were in the range of 48-62 μg/ml. The hemolysis caused by formulations was 1-2%. The spreading potential of the formulations (F1 and F5) over damaged skin model was remarkable. These results suggest that cu-SEDDS further enhanced the broad spectrum antileishmanial and antibacterial profile of curcumin and could be used for the treatment of cutaneous leishmaniasis and its associated secondary infections.

Introduction: Pseudomonas aeruginosa is one of the major pathogens associated with the acute tissue damage in patients having Diabetic Foot Ulcer (DFU). The treatment of such infections can be an uphill battle due to the serious resistance to all the mainstay antibiotics, owing to overzealous production of Extended-Spectrum Beta-Lactamases (ESBLs). Pakistan also has a high prevalence of diabetes and complications related to it, however genetic disposition of the pathogens remains underinvestigated., Aim: The main objective of the study was to determine the frequency of ESBLs in Multi-drug resistant P. aeruginosa from diabetic foot patients., Methods: The duration of the present study was one year and 100 patients having DFU were enrolled. All the pus samples were subjected to the bacterial culture, gram staining, catalase test, oxidase test and antimicrobial susceptibility pattern to various antibiotics for the confirmation of P. aeruginosa. Of 23 positive isolates of P. aeruginosa, 10 were ESBLs positive as detected by double disk diffusion test. The positive ESBL strain shows an increase of ≥5mm in the zone of inhibition of the combination discs in comparison to the alone ceftazidime disc., Results: The ESBLs positive strains were also tested for TEM-1, SHV-1, PER-1, and VEB-1, where: (07/10) strains carried SHV-1, (05/10) strains were positive for TEM-1, while none of the isolates were PCR-positive for PER-1 and VEB-1., Conclusion: The findings of the current study show a difference in the pattern of ESBL genes compared to that of other such endeavors. The present study also warrants the PCR-based detection of the type of ESBL as a potential factor to consider in deciding the therapeutic strategy at any point during the treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate the effect of fatty meal on intestinal alkaline phosphatase., Methods: The cross-sectional study was conducted at Khyber Medical University, Peshawar, Pakistan from March to April 2014 and comprised young healthy individuals 18-25 years of age. Whole blood samples were collected from the subjects in ethylenediaminetetraacetic acid anti-coagulated and plane serum tubes. For blood group analysis, blood group anti sera were used, while for serum alkaline phosphatase, a chemistry analyser was used. Alkaline phosphatase levels in the blood before and after breakfast were compared., Results: Of the 177 subjects, there were 139(78.5%) men and 38(21.4%) women. Mean fasting alkaline phosphatise level was 144.22+/-75.57, while mean random value was 174.15+/-96.70 (p=0.001)., Conclusions: Serum alkaline phosphatise must be analysed in fasting state early in the morning.

A series of 6-chloro-3-oxindole derivatives 1-25 were synthesized in high yields by the reaction of 6-chlorooxindole with different aromatic aldehydes in the presence of piperidine. All the synthesized compounds were isolated with E configuration. The structures were confirmed using spectroscopic techniques, including (1)H NMR and EIMS. These compounds showed varying degree of yeast α-glucosidase inhibition and seven were found as potent inhibitors of the enzyme. Compounds 2, 3, 4, 5, 6, 23, and 25 exhibited IC50 values 2.71±0.007, 11.41±0.005, 37.93±0.002, 15.19±0.004, 24.71±0.007, 17.33±0.001, and 14.2±0.002μM, respectively, as compared to standard acarbose (IC50, 38.25±0.12μM). Docking studies helped to find interactions between the enzyme and the active compounds. As a result of this study, oxindoles have been discovered as a new class of α-glucosidase inhibitors which have not been reported earlier., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Urease is an important enzyme both in agriculture and medicine research. Strategies based on urease inhibition is critically considered as the first line treatment of infections caused by urease producing bacteria. Since, urease possess agro-chemical and medicinal importance, thus, it is necessary to search for the novel compounds capable of inhibiting this enzyme. Several computational methods were employed to design novel and potent urease inhibitors in this work. First docking simulations of known compounds consists of a set of arylidine barbiturates (termed as reference) were performed on the Bacillus pasteurii (BP) urease. Subsequently, two fold strategies were used to design new compounds against urease. Stage 1 comprised of the energy minimization of enzyme-ligand complexes of reference compounds and the accurate prediction of the molecular mechanics generalized born (MMGB) interaction energies. In the second stage, new urease inhibitors were then designed by the substitution of different groups consecutively in the aryl ring of the thiobarbiturates and N, N-diethyl thiobarbiturates of the reference ligands.. The enzyme-ligand complexes with lowest interaction energies or energies close to the calculated interaction energies of the reference molecules, were selected for the consequent chemical manipulation. This was followed by the substitution of different groups on the 2 and 5 positions of the aryl ring. As a result, several new and potent diethyl thiobarbiturates were predicted as urease inhibitors. This approach reflects a logical progression for early stage drug discovery that can be exploited to successfully identify potential drug candidates.

Objective: To evaluate the antibacterial activity of the combination of different honey brands and methanolic fraction of Herba Ocimi Basilici using agar well diffusion assay., Methods: The antibacterial activity was determined against thirteen pathogenic bacterial clinical isolates including six gram negative (Klebsiella pneumonia, Pseudomonas aeroginosa, Escherichia coli, Salmonella typhi, Salmonella typhimirium, Xanthomonas campestris) and six gram positive strains (Enterococcus faecalis faecalis, Bacillus subtilis, Staphylococcus aureus, Clostridium perfringens type C, Clostridium perfringens type D, Clostridium chauvoei). Agar well diffusion method was used while zones of inhibition were measured with vernier scale., Results: At higher concentration, all the honey brands showed good to significant activity. The highest activity was observed for Hamdard brand honey (27.60 +/- 0.40) against Enterococcus faecalis., Conclusion: These results revealed that combinations of plant extracts of Herba Ocimi Basilici with honey can be used for the development of potent and novel antibacterial agents.

Benzophenonehydrazone Schiff bases 1-25 were synthesized and their in vitro antiglycation potential has been studied. Out of twenty-five compounds, thirteen showed varying degrees of antiglycation activity with IC50 values ranging between 25.7 - 305 μM, if compared with the standard rutin (IC50 = 70.5 ± 0.50 μM). Compounds 21 (2,3- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 25.7 ± 0.003 μM, 14 (diphenylmethanone N-[1-(2,4- dihydroxy-5-nitrophenyl)ethylidene]hydrazine) IC50 = 36.6 ± 0.004 μM, 6 (3,4-dihydroxybenzaldehyde N- (diphenylmethylene)hydrazine) IC50 = 49.5 ± 0.001 μM, 13 (diphenylmethanone N-[1-(2,5-dihydroxyphenyl)ethylidene] hydrazine) IC50 = 52.6 ± 0.023 μM, and 15 (diphenylmethanone N-[1-(3,4-dihydroxyphenyl)ethylidene]hydrazine) IC50 = 57 ± 0.002 μM, showed showed much better antiglycation potential superior to the standard rutin. The compounds 7 (2,5- dihydroxybenzaldehyde N-(diphenylmethylene)hydrazine) IC50 = 66 ± 0.002 μM, and 25 (diphenylmethanone N-[1-(2,5- dihydroxyphenyl)propylidene] hydrazine) IC50 = 67.9 ± 0.001 μM showed compareably good antiglycation activity to standard rutin. All compounds were characterized by spectroscopic techniques and gave satisfactory elemental analysis.

Background: Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization mass spectrometric technique, allowing the analysis of bio-molecules and other macromolecules. The matrix molecules require certain characteristic features to serve in the laser desorption/ionization mechanism. Therefore, only a limited number of compounds have been identified as ultraviolet- laser desorption/ionization (UV-LDI) matrices. However, many of these routine matrices generate background signals that useful information is often lost in them. We have reported flavones, coumarindione and benzimidazole derivatives as alternate UV-LDI matrices., Results: Thirty one compounds have been successfully employed by us as matrices for the analysis of low molecular weight (LMW) peptides (up to 2000 Da). Two peptides, bradykinin and renin substrate tetra-decapeptide were analyzed by using the newly developed matrices. The MS measurements were made after mixing the matrix solution with analyte by using dried droplet sample preparation procedures. The synthesized matrix materials showed better S/N ratios and minimal background signals for low mass range. Furthermore, pico molar concentrations of [Glu1]-fibrinopeptide B human could be easily analyzed with these matrices. Finally, BSA-digest was analyzed and identified through database search against Swiss-Prot by using Mascot., Conclusions: These results validate the good performance of the synthesized UV-laser desorption/ionization (LDI) matrices for the analysis of low molecular weight peptides.

Background: Telmisartan and atenolol are widely used in the management of essential hypertension. This study was conducted to compare the efficacy of these two drugs in management of patients of essential hypertension., Methods: Diagnosed patients of essential hypertension were selected. Therapeutic option (telmisartan/atenolol) was allocated to the patients by lottery method and they were divided into two groups. The patients were followed on subsequent visits (4 in total) and their sitting systolic and diastolic blood pressures were recorded., Results: Total number of 180 patients were divided into two treatment groups (i.e., telmisaran and atenolol). Forty percent were male and 60% were female. Majority of the patients were of age group 56-75 years. Telmisartan reduced systolic and diastolic blood pressure significantly compared to atenolol at the end of 8 weeks of treatment (p = 0.000 and 0.016 respectively)., Conclusion: Telmisartan 80 mg once daily is more effective than atenolol 50 mg once daily in lowering systolic and diastolic blood pressure at the end of 8 weeks of treatment.

Syntheses of thirty 2,4,6-trichlorophenylhydrazine Schiff bases 1-30 were carried out and evaluated for their in vitro DPPH radical and super oxide anion scavenging activities. Compounds 1-30 have shown a varying degree of DPPH radical scavenging activity and their IC50 values range between 4.05-369.30 µM. The compounds 17, 28, 18, 14, 8, 15, 12, 2, 29, and 7 exhibited IC50 values ranging between 4.05±0.06-24.42±0.86 µM which are superior to standard n-propylgallate (IC50=30.12±0.27 µM). Selected compounds have shown a varying degree of superoxide anion radical scavenger activity and their IC50 values range between 91.23-406.90 µM. The compounds 28, 8, 17, 15, and 14, showed IC50 values between 91.23±1.2-105.31±2.29 µM which are superior to standard n-propylgallate (IC50=106.34±1.6 µM).

Benzimidazole derivatives 1-24 have been synthesized and their in vitro β-glucuronidase inhibitory activitiy was evaluated. Compounds 15 (IC50=6.33+/-0.40 μM), 7 (IC50=22.0+/-0.33 μM), 2 (IC50=23.1+/-1.78 μM), 17 (IC50=23.9+/-1.46 μM), and 3 (IC50=33.8+/-1.61 μM) showed more potent β-glucuronidase inhibitory activity than the standard (D-saccharic acid 1,4 lactone, IC50=48.4+/-1.25 μM). This study has identified a new series of potential β-glucuronidase inhibitors. A structure-activity relationship has also been studied.

2,4,6-Trichlorophenyl hydrazones 1-35 were synthesized and their in vitro antiglycation potential was evaluated. Compounds 14 (IC50 = 27.2 ± 0.00 μM), and 18 (IC50 = 55.7 ± 0.00 μM) showed an excellent activity against glycation of protein, better than the standard (rutin, IC50 = 70 ± 0.50 μM). This study thus identified a novel series of antiglycation agents. A structure-activity relationship has been studied, and all the compounds were characterized by spectroscopic techniques.

Disulfides 1-30 have been synthesized and their in vitro leishmanicidal activity has been evaluated. Compounds 18 (IC50 = 2.70 ± 0.044 μM), 19 (IC50 = 2.85 ± 0.02 μM), 20 (IC50 = 2.92 ± 0.01 μM), 26 (IC50 = 3.69 ± 0.01 μM), 21 (IC50 = 4.45 ± 0.029 μM), and 29 (IC50 = 4.46 ± 0.025 μM) showed a remarkable leishmanicidal activity if compared with standard pentamidine (IC50 = 5.09 ± 0.04 μM). This study has discovered a series of possible molecules as antileishmanial agents. A structure-activity relationship study has also been carried out. The structures of all the synthesized compounds were identified by using spectroscopic techniques, including 1H-NMR and EI MS.