Search

Ashfaq Ahmad, 1, 2 Farhat Ullah, 2 Abdul Sadiq, 2 Muhammad Ayaz, 2 Muhammad Saeed Jan, 2 Muhammad Shahid, 1 Abdul Wadood, 3 Fawad Mahmood, 1 Umer Rashid, 4 Riaz Ullah, 5 Muhammad Umar Khayam Sahibzada, 1 Ali S Alqahtani, 5 Hafiz Majid Mahmood 6 1Department of Pharmacy, Sarhad University of Science & Technology, Peshawar, KPK, Pakistan; 2Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000, KP, Pakistan; 3Department of Biochemistry, UCS, Shankar Abdul Wali Khan University, Mardan 23200, Pakistan; 4Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan; 5Department of Pharmacognosy, Medicinal, Aromatic and Poisonous Plants Research Center (MAPRC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 6Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaCorrespondence: Abdul SadiqDepartment of Pharmacy,Faculty of Biological Sciences, University of Malakand, Chakdara 18000, KP, PakistanTel +92 301-2297-102Email sadiquom@yahoo.comAshfaq AhmadDepartment of Pharmacy, Sarhad University of Information Technology, Peshawar, PakistanEmail ashfaqpharma123@gmail.comIntroduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays.Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver–Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis–Menten kinetics.Results: In AChE inhibitory assay, compounds 1 and 2 exhibited IC 50 of 343.45 and 422.98 μM, respectively, against AChE enzyme. Similarly, both the compounds showed IC 50 of 276.86 and 357.91 μM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC 50 of 157.71 and 471.79 μM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC 50 values of 297.98, 332.94, and 825.92 μM against DPPH, ABTS, and H 2O 2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2.Conclusion: Both succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.Keywords: succinimides, Alzheimer’s disease, cholinesterase, antioxidant, glucosidase, molecular docking

Sumaira Naz,1 Muhammad Zahoor,1 Muhammad Naveed Umar,1 Barkat Ali,1,2 Riaz Ullah,3 Abdelaaty A Shahat,3,4 Hafiz Majid Mahmood,5 Muhammad Umar Khayam Sahibzada6 1Department of Chemistry, University of Malakand Chakdara, Dir Lower, Kpk 18800, Pakistan; 2Department of Chemistry, GC University Faisalabad, Faisalabad, Punjab, Pakistan; 3Medicinal, Aromatic and Poisonous Plants Research Center (MAPRC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 4Phytochemistry Department, National Research Centre, Giza, Egypt; 5Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 6Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Kpk 25000, PakistanCorrespondence: Muhammad Umar Khayam SahibzadaDepartment of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK 25000, PakistanEmail umar.sahibzada@gmail.comMuhammad ZahoorDepartment of Chemistry, University of Malakand Chakdara, Dir Lower, KPK 18800, PakistanEmail mohammadzahoorus@yahoo.comBackground: In this study, 2 symmetrical and 3 unsymmetrical thioureas were synthesized to evaluate their antioxidant, antibacterial, antidiabetic, and anticholinesterase potentials.Methods: The symmetrical thioureas were synthesized in aqueous media in the presence of sunlight, using amines and CS2 as starting material. The unsymmetrical thioureas were synthesized using amines as a nucleophile to attack the phenyl isothiocyanate (electrophile). The structures of synthesized compounds were confirmed through H1 NMR. The antioxidant potential was determined using DPPH and ABTS assays. The inhibition of glucose-6-phosphatase, alpha amylase, and alpha glucosidase by synthesized compounds was used as an indication of antidiabetic potential. Anticholinesterase potential was determined from the inhibition of acetylcholinesterase and butyrylcholinesterase by the synthesized compounds.Results: The highest inhibition of glucose-6-phosphatase was shown by compound V (03.12 mg of phosphate released). Alpha amylase was most potently inhibited by compound IV with IC50 value of 62 μg/mL while alpha glucosidase by compound III with IC50 value of 75 μg/mL. The enzymes, acetylcholinesterase, and butyrylcholinesterase were potently inhibited by compound III with IC50 of 63 μg/mL and 80 μg/mL respectively. Against DPPH free radical, compound IV was more potent (IC50 = 64 μg/mL) while ABTS was more potently scavenged by compound I with IC50 of 66 μg/mL. The antibacterial spectrum of synthesized compounds was determined against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Agrobacterium tumefaction and Proteus vulgaris). Compound I and compound II showed maximum activity against A. tumefaction with MIC values of 4.02 and 4.04 μg/mL respectively. Against P. vulgaris, compound V was more active (MIC = 8.94 μg/mL) while against S. aureus, compound IV was more potent with MIC of 4.03 μg/mL.Conclusion: From the results, it was concluded that these compounds could be used as antibacterial, antioxidant, and antidiabetic agents. However, further in vivo studies are needed to determine the toxicological effect of these compounds in living bodies. The compounds also have potential to treat neurodegenerative diseases.Keywords: picolylamine, symmetrical thioureas, enzyme inhibition, anti-diabetic, antioxidant, Alzheimer’s disease, antibacterial

Wasim Ul Bari,1 Mohammad Zahoor,1 Alam Zeb,2 Muhammad Umar Khayam Sahibzada,3 Riaz Ullah,4 Abdelaaty A Shahat,4,5 Hafiz Majid Mahmood,6 Irfan Khan11Department of Chemistry, University of Malakand, Dir Lower, Chakdara, KPK 18800, Pakistan; 2Department of Biotechnology, University of Malakand, Dir Lower, Chakdara, KPK 18800, Pakistan; 3Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK 25000, Pakistan; 4Medicinal, Aromatic and Poisonous Plants Research Center (MAPRC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 5Phytochemistry Department, National Research Centre, Giza, Egypt; 6Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaCorrespondence: Mohammad ZahoorDepartment of Chemistry, University of Malakand Chakdara, Dir Lower, KPK 18800, PakistanEmail mohammadzahoorus@yahoo.comMuhammad Umar Khayam SahibzadaDepartment of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK 25000, PakistanEmail umar.sahibzada@gmail.comBackground: Traditionally, Grewia optiva is widely used for the treatment of many diseases like dysentery, fever, typhoid, diarrhea, eczema, smallpox, malaria and cough.Methods: Shade-dried roots of G. optiva were extracted with methanol. Based on HPLC results, chloroform and ethyl acetate fractions were subjected to silica column isolation and four compounds: glutaric acid (V), 3,5 dihydroxy phenyl acrylic acid (VI), (2,5 dihydroxy phenyl) 3’,6’,8’-trihydroxyl-4H chromen-4’-one (VII) and hexanedioic acid (VIII) were isolated in pure form. Ellman’s assay was used to determine the anticholinesterase potential of isolated compounds while their antioxidant potential was estimated by DPPH and ABTS scavenging assays.Results: Amongst the isolated compounds, VI and VII exhibited excellent percent inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) (83.23±1.11, 82.72±2.20 and 82.11±2.11, 82.23±1.21, respectively, at 1000 μg/mL) with IC50 of 76, 90, 78 and 92 μg/mL, respectively. Highest percent radicals scavenging against DPPH and ABTS (87.41±1.20 and 86.13±2.31) with IC50 of 64 and 65 μg/mL, respectively, were observed for compound VII. Molecular docking studies also supported the binding of compound VI and VII with the target enzyme. The para-hydroxyl group of the phenolic moiety is formed hydrogen bonds with the active site water molecule and the side chain carbonyl and hydroxyl residues of enzyme.Conclusion: The isolated compounds inhibited the DPPH and ABTS-free radicals, and AChE and BChE enzymes. It was concluded that these compounds could be used in relieving the oxidative stress and pathological symptoms associated with excessive hydrolysis of acetyl and butyryl choline. The results of the study were supported by docking studies for compounds VI and VII.Keywords: G. optiva, antioxidant, acetylcholinesterase, butyrylcholinesterase, molecular docking

In the present study four bacterial strains Escherichia Coli, Salmonella typhi, Shiegella and Pseudomonas aeruginosa were used to evaluate their dye decolorization/degradation ability. Out of these bacterial strains Pseudomonas aeruginosa exhibited high potential for selected dye decolorization and hence it was used in subsequent experiments. The effect of dye concentration, pH, temperature, time, glucose and sodium chloride concentrations on decolorization were also studied to determine the optimal conditions required for maximum decolorization/degradation of selected dye by Pseudomonas aeruginosa. Maximum decolorization was observed at: 0.01 mg/L dye concentration, pH 10, temperature 45and#176;C, 0.1 mg/L glucose concentration, 0.1 mg/L sodium chloride concentration and 3 days incubation period at 37and#176;C. The metabolites formed after degradation by selected bacteria at optimum conditions were isolated and characterized by FTIR and mass spectrometry. In the mass spectra molecular ion peak was not observed and it was difficult to draw a conclusion from it. However, FTIR spectra provided some valuable information. The peaks at 1301.8 cm-1 for C-N and 1231.5 cm-1 for O-H stretch observed for original dye were completely absent in the decolorized products. The disappearance of C-N (part of the porphyrin ring system) peak in FTIR spectra shows that the porphyrin ring has been destroyed by bacteria. The extensive fragmentations in the mass spectra also confirm the degradation of the dye parental structure.

The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region.