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Despite being routinely used for pain management, opioid use is limited due to adverse effects such as development of tolerance and paradoxical pain, including thermal hyperalgesia and mechanical allodynia. Evidence indicates that continued morphine administration causes increased expression of proinflammatory mediators such as tumor necrosis factor-alpha (TNF-α). The objectives of the present study were to determine the effects of B1 (N -[(1 H -benzimidazol-2-yl)methyl]-4-methoxyaniline) and B8 (N -{4-[(1 H -benzimidazol-2-yl)methoxy]phenyl}acetamide), benzimidazole derivatives, on thermal nociception and mechanical allodynia during repeated morphine (intraperitoneal; 5 mg/kg twice daily for 6 days)-induced paradoxical pain and TNF-α expression in the spinal cord in mice. Our data indicate that administration of benzimidazole derivatives attenuated morphine-induced thermal hyperalgesia and mechanical allodynia. Benzimidazole derivatives also reduced TNF-α expression in mice. Taken together, these results suggest that benzimidazole derivatives might be useful for the treatment of neuroinflammatory consequences of continued morphine administration and could be potential drug candidates for the management of opioid-induced paradoxical pain. [ABSTRACT FROM AUTHOR]

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Plants mediated synthesis of noble metal nanoparticles is encountered as a clean, environment friendly, lucrative and benign loom. The current study consists of clean and green synthesis of Silver nanoparticles (AgNPs). Phytoconstituents from Longan (Euphorbia longana Lam . ) fruit peel were used to reduce Ag + into AgNPs. Different analytical techniques i.e. UV–vis Spectroscopy, X-ray diffraction spectroscopy (XRD), electron dispersive X-ray (EDX), High-resolution transmission electron microscopy (HRTEM) and Fourier transform infrared spectroscopy (FTIR) were used to analyze the synthesized AgNPs. AgNPs have localized surface plasmon resonance (LSPR) peak at 445 nm which is confirmed by UV–vis spectroscopy. HRTEM showed that the prepared AgNPs are spheroid in shape and well dispersed while XRD results showed that the AgNPs are face centered cubic crystalline. EDX confirmed the elemental composition of AgNPs. The antiproliferative response of AgNPs was assayed by an exhaustive MTT assay. AgNPs showed potent anticancer activity (88%) against breast cancer cells MCF-7 . Moreover, the green produced AgNPs effectively scavenged 91% of the stable and harmful 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical which confirms its' efficient antioxidant nature. AgNPs have profound photocatalytic degradation (99%) of methylene blue in a short period of time (7 min). The noteworthy biological and photocatalytic responses of the green and cleanly produced AgNPs are encountered to their well dispersion, petite volume and round shaped structure . [ABSTRACT FROM AUTHOR]

Some new pyrimidine derivatives have been synthesised by electrochemical oxidation of catechol (1a) in the existence of 2-mercapto-6-(trifluoromethyl) pyrimidine-4-ol (3) as a nucleophile in aqueous solution using Cyclic Voltammetric and Controlled Potential Coulometry. The catechol has been oxidised to o-quinone through electrochemical method and participative in Michael addition reaction, leading to the development of some new pyrimidine derivatives. The products were achieved in good yield with high pureness. The mechanism of the reaction has been conformed from the Cyclic Voltammetric data and Controlled Potential Coulometry. After purification, the compounds were characterised using modern techniques. The synthesised materials were screened for antimicrobial actions using Gram positive and Gram negative strain of bacteria. These new synthesised pyrimidine derivatives showed very good antimicrobial activity. [ABSTRACT FROM AUTHOR]

Caralluma edulis (Edgew.) Benth. ex Hk.f. (Asclepiadaceae) is traditionally used for the management of rheumatism. The current study aimed to assess the anti-inflammatory effect of Caralluma edulis, to explain its medicinal use in inflammatory ailments. Caralluma edulis crude extract (Ce.Cr) was investigated in acute (carrageenan and xylene mediated) and chronic (formalin evoked) models of inflammation in mice. Ce.Cr which shows the presence of alkaloids, glycosides, flavonoids, saponins, phenols, terpenes and tannins caused dose-dependent (100, 300 and 1000 mg/kg) reduction of the carrageenan, xylene and formalin-induced inflammation (P < 0.05, P < 0.001 vs. saline group). At the lower dose of 30 mg/kg it was effective in inhibiting the xylene mediated ear edema. No mortality observed with Ce.Cr upto 5 g/kg. This study reveals that Caralluma edulis possess therapeutic ability to reduce inflammation, hence proving its potential to be used as an alternative medicine in the management of inflammatory disorders and also validate its folkloric use in treatment of rheumatism. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possible hepatoprotective potential of Parthenium hysterophorus crude extract (Ph.Cr) against carbon tetrachloride (CCL4)- and paracetamol-induced hepatotoxicity in rabbits. Methods: Twenty rabbits were divided into five groups of four rabbits each. Group 1 served as normal control and received normal saline (5 mL/kg). Group 2 received normal saline followed by CCL4 (0.75 mL/kg p.o dose) after 1 h. Groups 3 and 4 received Ph.Cr at doses of 15 and 30 mg/kg po, respectively, for 7 days followed by one dose of CCL4, 2 h after the last extract dose (0.75 mL/kg, sc). Group 5 received silymarin as reference standard at a dose of 100 mg/kg orally for 7 days followed by one dose of CCL4 (0.75 mL/kg, sc), 2 h after the last drug dose. The effect of the extract on potassium (K+)- induced contractions in isolated rabbit jejenum was also evaluated. At the end of the study, the animals were sacrificed and their liver architecture examined microscopically. Results: Pre-treatment of rabbits with Ph.Cr reduced ALT, ALP and TB levels (p < 0.05, p < 0.01, p < 0.001) dose dependently. Hepatoprotective data indicate that Ph.Cr markedly reduced CCL4- and paracetamol-induced toxicity by preserving the histological architecture of the liver tissue at near normal. In isolated rabbit jejunum tissue, Ph.Cr relaxed high K+ (80 Mm)-induced contractions in a concentration-dependent (0.03 - 10 mg/mL) manner like that caused by silymarin. Conclusion: In the light of the results obtained, Parthenium hysterophorous possesses hepatoprotective activity against CCL4- and paracetamol-induced hepatic damage, possibly mediated via its antioxidant and Ca++ antagonist mechanisms. [ABSTRACT FROM AUTHOR]

In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis. Nepetolide concentrationdependently (1.0-1000 mg/mL) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus. In brine shrimp's lethality model, nepetolide potently showed cytotoxic effect, with LC50 value of 8.7 mg/mL. When evaluated for antitumor activity in potato disc tumor assay, nepetolide exerted tumor inhibitory effect of 56.5 ± 1.5% at maximum tested concentration of 1000 mg/mL. Nepetolide at 20 mg/kg reduced carrageenaninduced inflammation (P < .001 vs. saline group) in rat paw. Nepetolide dose-dependently (100--500 mg/kg) decreased acetic acid evoked writhes, as exhibited by diclofenac sodium. In-silico investigation of nepetolide was carried out against cyclooxygenase-2, epidermal growth factor receptor and lipoxygenase-2 targets. Virtual screening through Patchdock online docking server identified primarily hydrophobic interactions between ligand nepetolide and receptors proteins. Enhanced hydrogen bonding was predicted with Autodock showing 6--8 hydrogen bonds per target. These results indicate that nepetolide exhibits antioxidant, antibacterial, cytotoxic, anticancer, anti-inflammatory and analgesic activities and should be considered as a lead compound for developing drugs for the remedy of oxidative stressinduced disorders, microbial infections, cancers, inflammations and pain. [ABSTRACT FROM AUTHOR]

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A series of six novel benzimidazole-pyrazole hybrid molecules was synthesized and characterized using elemental analysis (CHN) and spectroscopic methods (HNMR, FT-IR). All the synthesized compounds were evaluated for their in vivo anti ulcerogenic activity using Albino rats (weighing 180-220 g). The interactions between the compounds and active site residues of H/K ATPase were investigated by molecular docking studies using autodock vina 4.0. SCH28080 was used to validate the docking results. Also the drug likeliness of these compounds was predicted using Molinspiration server in light of Lipinski's rule of five. All the six synthesized compounds exhibited higher anti-ulcer activity as compared to omeprazole. These novel hybrid compounds showed comparable anti-ulcer potential of 72-83% at dose level of 500 µg/kg, whereas omeprazole showed 83% anti-ulcer activity at dose level of 30 mg/kg. The results clearly indicate that these novel benzimidazole-pyrazole hybrids can present a new class of potential anti ulcer agents and can serve as new anti-ulcer drugs after further investigation. [ABSTRACT FROM AUTHOR]

Glucoside derivatives of 1,3,4-oxadiazoles and 4-amino-1,2,4-triazoles: N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-5-(4-florophenyl)-1,3,4-oxadiazole-2-thione (1a), N-(2,3,4,6-tetra-Oacetyl- β-D-glucopyra nosyl)-5-(3,4,5-trimethoxylphenyl)-1,3,4-oxadiazole-2-thione (1b), N-(2,3,4,6-tetra-O-acetyl-β- D-glucopyra nosyl)-4-amino-5-(2-chlorophenoxyl methyl)-1,2,4-triazole-3-thione (2a) and N-(2,3,4,6-tetra-O-acetylβ- D-glucopyranosyl)-4-amino-5-(2-bromophenoxylmethyl)-1,2,4-triazole-3-thione (2b) were synthesized and characterized by IR, ¹H-NMR, 13C-NMR and mass spectral techniques. (1b) has highest antioxidant potential. Test compounds have good activity against Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Salmonella typhae, Klebsilla pneumonia, Candida glabrata and exhibited mild to moderate cytotoxic effect. (1a) and (2b) showed 73.9 ± 2.5% and 75.4 ± 1.5% tumor inhibitory action respectively. (1a) and (2a) possess antileishmanial activity with IC50 value of 0.060 ± 0.00 and 0.065 ± 0.01 mg/mL. All compounds reduced carrageenan-induced paw edema in mice. Virtual screening of (1a) and (2b) against DNA gyrase, topoisomerase-IV, lanosterol-14-alpha demethylase, cyclooxygenase-2 and epidermal growth factor receptor tyrosine kinase gives total energy values upto -405.77 Kcal/mol. [ABSTRACT FROM AUTHOR]