VOLUME 45, NO6, DEC-2023

Design, Synthesis and Biological Evaluation of Several Novel 4-aminoquinazoline Derivatives as Potent Anti-Tumor Agents

A series of 4-aminoquinazoline derivatives were designed and synthesized as epidermal growth factor receptor (EGFR) inhibitors in our group. The bioassay results showed all the target compounds possessed potential anti-tumor activities against on A549 and H1975 cell lines. The IC50 values of 8.35 (for A549) and 19.18 μM (for H1975) exhibited remarkable inhibitory activity of compound 7d, which were better compared to the positive control Afatinib (IC50 = 10.41 μM for A549, IC50 = 24.96 μM for H1975). In addition, the molecular docking and ADME prediction of compound 7d was carried out. The experimental results show the compound 7d is worth to further research and discuss.read more

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Liang-Liang Chi, Zhi-Qiang Cai, Bo Wang, Wei-Tao Qin, Ya-Nan Wang, Qiao-Qiao Feng and Wen-Jie Ren

Synthesis and Characterization of Sweet Potato Starch Biocomposite Incorporated with ZnO Nanoparticles

The rapid rise in the production of hazardous waste in the environment, particularly single-use plastics, has prompted the development of sustainable yet cost-effective alternatives. This research aims to create bioplastic films using renewable energy sources. To prevent toxic side products, the composite bioplastics synthesized from sweet potato starch are incorporated with biogenically synthesized ZnO NPs. Biocomposite films were characterized by their morphology, water vapor permeability (WVP), biodegradability, thermal and mechanical properties. It was noted that the ZnO NPs had substantial effects on the tensile properties of the nanocomposite films. The addition of ZnO NPs to the starch bioplastic films considerably enhanced tensile strength from 1.41 to 2.26 MPa, elongation from 78.20 to 114.91%, and Young’s modulus from 1.62 to 2.40 MPa. The incorporation of ZnO NPs lowered the degree of WVP and film solubility value compared to those of the starch films. The bioplastic film incorporated with ZnO NPs had effective UV absorption and transparency. The shift in the peaks in the FT-IR spectra confirmed the relationship between the polymer matrix and the ZnO NPs. Thermal degradation of bio nanocomposite at 339.60 °C is shown by a consistent reduction in TGA between 240 °C and 410 °C. The high melting temperature (Tm) of 144 oC for starch film and 201.86 oC for bio nanocomposite was found using DSC analysis. SEM analysis revealed that biocomposite films had better compatible morphologies with small cracks and the roughness of films increased with the addition of ZnO NPs content. The biodegradability of the biocomposite films was analyzed through the soil burial method. The bioplastic produced in this study has the potential to be a viable alternative to existing conventional plastics in the packaging industry.read more

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Saira Iqbal, Arjumand Iqbal Durrani and Ashi Rashid

A Sensitive Spectrophotometric Determination of Silver (I) with Blue Tetrazolium Chloride

Silver(I)-assisted reduction of Blue tetrazolium chloride (3,3′-(3,3′-dimethoxy[1,1′-biphenyl]-4,4′-diyl)-bis(2,5-diphenyl-2H-tetrazolium) dichloride, BTC) by semicarbazide hydrochloride (SCH) was investigated in water-chloroform medium. The obtained colored products can be used for the visual detection and sensitive liquid-liquid extraction–spectrophotometric determination of Ag(I). Under the optimum conditions the calibration curve (which can be best approximated by a third-order polynomial; R2=0.9990) has two linear segments. For Ag(I) concentrations up to 0.011 g/ml, the linear regression equation had an intercept that was statistically indistinguishable from zero. The limit of detection, limit of quantitation, and molar absorptivity coefficient at λmax=573 nm were 0.6 ng/ml, 2 ng/ml and 1.2×106 l/(molcm), respectively. The regression equation of the second linear segment (0.021–0.028 g/ml) was A = 200γ – 3.5 (R2=0.9989), where γ is the concentration in μg/ml. The relative standard deviation at the 22 ng/ml level (n = 5) was 3.8 %. The effect of concomitant ions was studied, and the analysis of real samples tested the applicability of the developed procedure.read more

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Vidka Vassileva Divarova, Denitsa Dimitrova Kiradzhiyska and Kiril Blazhev Gavazov

Synthesis, Spectral Characterization and Biological Evaluation of Platinum (II) Complexes of 1,3,4-oxadiazole-2-thione from Fatty Acids

The fatty acid can be separated by separation techniques according to degree of unsaturated and chain length. In this paper fatty acid methyl esters are separated by Argentation Chromatography then converted to 1, 3, 4-oxadiazole. Platinum complexes of 1, 3, 4-oxadiazole are synthesized and Oxadiazole-2-thione ligands containing C=N and C=S groups as coordination sites may behave as a monobasic monodentate ligand. Antioxidant activity of complexes are measured by DPPH assay and in vitro cytotoxicity of the synthesized complexes measured against two human cancer cell line by MTT assay. In general, both MCF7 and A549 cell lines are sensitive to all the tested compounds. The Pt-complexes that contain unsaturated fatty acid are most active on the A549 cell line and important for human lung cancer, while the Pt4 has activity on MCF7 cell line and is important for human breast cancer.read more

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Saber Salim, Mohamad Hikmat and Aziz Madzlan

Papaverine Derivatives, a Potent Inhibitor of Neuroinflammation in Epileptic Seizures, A Pharmacological and In-Silico Approach Against TNF-α as a Targeted Receptor

Epilepsies are a heterogeneous group of disorders expressed in terms of propensity to experience spontaneous recurrent seizures attack. Verapamil, a synthetic amide derivative containing papaverine, is a calcium channel blocker that significantly reduces the frequency of seizures. Based on this, the current work was planned to concentrate on the synthesis of more recent papaverine derivatives that contain amides. Z1 and Z2 were created using synthesis. Following synthesis, docking analysis was performed, and bond energies were computed to determine their binding affinities against the TNF- α protein in particular because it upregulates neuroexcitation, enables excessive calcium absorption, and ultimately results in neurotoxicity. Later, compounds were examined for their antioxidant and antiepileptic properties. Elisa and H&E staining were also carried out, and the results demonstrated that treatment with papaverine derivatives reduced the biochemical and immunohistochemical changes brought on by pentylenetetrazol that were related to TNF- α.read more

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Zeenia Tariq, G.A. Miana, Madiha Kanwal, Muhammad Fahim and Sumra Malik

Phytochemical Composition and Antibacterial Properties of Surface Extracts of Six Salvia Species

The chemistry and biological activity of cuticular waxes and the secondary metabolites produced in the indumentum of different plant organs has been attracting the interest of botanists. This work was aimed to investigate the chemistry and antibacterial activity of the surface extracts (SE) of different organs of six Salvia species. The cuticles and indumenta of the leaves, calyxes, and stems of Salvia atropatana Bunge., S. lachnocalyx Hedge., S. ceratophylla L., S. palaestina Benth., S. persepolitana Boiss., and S. hydrangea DC. ex Benth. were extracted with dichloromethane. The SEs were analyzed using gas chromatography-mass spectrometry (GC/MS). The antibacterial activity of each extract was assessed against Escherichia coli, Staphylococcus epidermidis, and Bacillus subtilis strains using the agar disc diffusion bioassay. The yields of extracts were in the range from 1.1- 2.3% w/w, while the detected compounds constituted 59.3-95.4% of the total extract composition. All species except S. persepolitana contained the sesquiterpenes, including β-caryophyllene (0.5-19.5%) and germacrene D (0.4-12.9%), while sclareol (2.1-75.6%) was the major labdane diterpenoid in the examined Salvia species excepting S. hydrangea. In addition to terpenoids, the analyzed SEs contained long-chain n-alkanes, fatty acids, alcohols, and aldehydes in the range from 4.8-78.5%. E. coli was the most susceptible microorganism to the tested extracts of S. persepolitana calyxes and stems (20 and 18 mm) and the S. lachnocalyx stems (17 mm), respectively. The antibacterial properties of the SEs of the plants suggested their protective role against pathogenic microorganisms, which can be attributed to their major phytochemicals such as sclareol and abienol.read more

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Somayeh Zare, Maryam Parish, Mehdi Zare and Amir Reza Jassbi

Synthesis and Antimicrobial Activity of a Number of 3-substituted-8-allylbenzoxazines and their Hydrobromic Salts

In this study, novel 1,3-benzoxazines 3a–d were synthesized starting from 2-allylphenol (2), formaldehyde and primary amines under Mannich reaction conditions, as well as their ammonium salts 4a–d, which were prepared by reaction of compounds 3a–d with HBr. As primary amines aniline, propylamine, n-hexylamine and n-octylamine were used. Synthesized heterocyclic compounds and their ammonium salts (3a–d and 4a–d) were characterized by elemental analysis, IR and NMR spectra. The antimicrobial activity of the synthesized compounds 3a–d and 4a–d at concentration 15 and 30 mgL-1 against microorganisms (Staphylococcus aureus NCTC6571, Staphylococcus aureus ATCC®25923, Escherichia coli ATCC®25922, Candida albicans NSTC - 3255/ATCC2091, Shigella flexneri ATCC®12022, Salmonella enterica ATCC®13076, and Aspergillus niger [isolate obtained from water]) was studied by the disk-diffuse method. It was found that compounds 3a–c are very effective against bacteria Staphylococcus aureus - NCTC 6571, Staphylococcus aureus ATCC®25923, Escherichia coli ATCC®25922, Shigella flexneri ATCC®12022, and Salmonella enterica ATCC®13076, but slightly effective against Candida albicans and Aspergillus niger. However, analysis revealed that the surfactants 4a–d have antimicrobial activity against all the above microorganisms, i.e., 4a–d have both bactericidal and fungicidal activity, which is explained by the present in its structure of the bromine anion, an ammonium fragment and a multiple bond. For comparison, as references at the identical concentration (30 mgL-1) and conditions amoxicillin and fluconazole were used. It was revealed, that the substances 4a–d, in comparison with the references used, are much higher in bactericidal and fungicidal effectiveness. Bactericidal efficacy was also confirmed by electron microscopy studies of Escherichia coli ATCC®25922 cells in the present of heterocyclic compound 4c (contain in the structure N-hexyl and allyl fragments) and amoxicillin (reference). It was found that, in the present of the synthesized compound 4c complete destruction of Escherichia coli ATCC®25922 cells was carried out (unlike to the presence of amoxicillin, used as reference).read more

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Gunay Muzakir Mehdiyeva, Musa Rza Bairamov, Eldar Kochari Gasimov, Fuad Huseynali Rzayev

The Chemical Composition and Antidiabetic, Neuroprotective and Cytotoxic Activities of Soft Hulls (Mesocarp) of Pistachio (Pistacia vera) Fruits

Pistachio (Pistacia vera L.) is an important cultivated plant in the Southeastern Anatolia region and its fruits are widely used in the food industry. The previous studies mostly focused on the food minerals and components. However, there is no study on chemical components and biological activity of the soft hulls of the pistachio fruits. In this study, it was focused on the acetone and water extracts of the soft hulls of pistachio fruits. Hence, the acetone extract was subjected to sephadex LH-20 column chromatography and fractioned into five fractions (Frs. A-E) according to molecular weight of components. A triterpen compound isolated from the Fr. B by crystallation method and its chemical structure was characterized as masticadienonic acid by spectroscopic methods. The fractions contain a mixture of the anacardic acids 13:1, 15:2, 15:1 and 17:1 and their derivatives according to their spectroscopic data and GC-MS analysis. Shikimic acid used in the synthesis of the oseltamivir, antiviral agent was also purified at high yield (14.36%) from the water extract of the soft hulls of pistachio fruits. In order to explore the antidiabetic properties of the pure compounds, the extracts and the fractions, their inhibition effects were determined on the activities of digestive enzymes (α-glucosidase and α-amylase). All of the extracts, masticadienonic acid and the fractions containing the anacardic acids strongly inhibited the α-glucosidase activity much more than acarbose. However, all applications exhibited much weaker inhibitory properties againts α-amylase, as compaired to the inhibition effect of the acarbose. Furthermore, the treatments of mesocarps of Pistachio fruits acted as much weaker inhibitors against AChE, whereas the acetone extract and its fractions containing different rates of anacardic acids were powerful agents against BChE as strong as neostigmine and galantamine. The cytotoxic activities of the extracts and the compounds against HUVEC, A549 and H1299 cells were also determined using the MTT analysis method and it was determined that the acetone extract and the compounds, masticadienonic and shikimic acids showed cytotoxic effects on the cellsread more

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Mehmet Akyuz, Lawali Yabo-Dambagi, Basak Simitcioglu, Isik Didem Karagoz, Tuba Aydin, Gonca Gokdemir, Ahmet Cakir and Cavit Kazaz

Phytochemical and In Vitro Biological Evaluation of Roots of Malvastrum coromandelianum (L.) Garcke

Malvastrum coromandelianum (L.) Garcke is a medicinal plant, employed traditionally for the treatment of different human illnesses. This study has been planned to study the chemical and biological aspects of the roots of the plant, using chemical and instrumental analytical techniques. Standard reported protocols were used for phytochemical screening of the crude extract, indicating the presence of terpenoids, steroids, flavonoids, and alkaloids classes of compounds. The extract was analyzed through Gas Chromatography-Mass Spectrometry (GC-MS) to confirm the presence of specific phytochemicals. The extract exhibited biological activities at good to moderate levels and was found to be non-toxic. Moderate inhibitory potential was observed against Aspergillus niger, Fusarium solani, Candida albicans, Klebsiella pneumoniae, Bacillus subtilis, Proteus mirabilis, Escherichia coli, and Staphylococcus aureus. At a concentration of 1000 μg/ml the crude extract showed 67 % inhibition of the Leishmania tropica promastigotes. The extract also displayed moderate radical scavenging activity. Interestingly, it showed lower red blood cell hemolysis (28%) at the highest concentration. The biological potential of the crude extract may be credited to these metabolites, as most of them have been previously reported to have the same activities.read more

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Sheema, Salman Zafar, Nazif Ullah, Ishaq khan, and Ghias ud din

Binding Pattern Analysis of Different Allosteric Inhibitors of Hepatitis C Virus (HCV) Polymerase

To the best of our knowledge, the current study could be considered the first comprehensive one based on the application of molecular docking on the non-nucleoside thumb and palm inhibitors to nonstructural NS5B protein for the detailed evaluation of their binding patterns in the corresponding binding regions in the protein. Non-nucleoside thumb and palm inhibitors were docked into the thumb and palm sites of the nonstructural NS5B protein which is the RNA-dependent RNA polymerase, respectively. Two docking programs, AutoDock 4.2 and AutoDock Vina were employed for the docking of thumb inhibitors (filibuvir and lomibuvir) and palm inhibitors (dasabuvir and nesbuvir) into the respective binding region. The preliminary analysis of the docking performance demonstrated that AutoDock Vina was suitable for the docking of large flexible molecules as deduced from the alignment of docking conformations in all cases. Based on the docking calculation, the interaction pattern analysis was carried out for all the inhibitors which were found to reside in the respective binding region. Before the interaction pattern analysis, the best docking pose was selected based on the high binding affinity value. The interaction pattern analysis of the inhibitors revealed that hydrogen bonding and hydrophobic contacts with amino acid residues of the respective binding region were the leading force in the stabilization of these inhibitors besides other interactions. The interaction pattern analysis based on the docking calculation was also realized to be the meaningful approach to figuring out the relative stability of the protein-ligand complex formed after the inhibitor binding which eventually led to assessing the inhibitory potential of these inhibitors and could also be helpful for the future inhibitor design.read more

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Marium Bibi