Antinociceptive Activity Of Compounds Research Articles

One pot synthesis of 5-hydroxyalkylated thiadiazine thiones: Implication in pain management and bactericidal properties

The synthesis of a new series of thiadiazine thiones including 5-(2-hydroxyethyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (1–5), 5-(2-hydroxypropyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (6–8), 3,5-dipropyl-1, 3, 5-thiadiazine-2-thione (9) and (2-(5-alkyl/aryl-6-thioxo-1, 3, 5-thiadiazine-3-yl) alkyl acetate/benzoate) (10–17) was accomplished via one pot reaction. The structures of the synthesized compounds were characterized through NMR and Mass spectrometry. The anti-nociceptive activity of compounds was performed on BALB/C mice by hot plate method, where compounds 3, 5 (50 μg/kg), and 8 (50, 100 μg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time of 15, 30, and 60 min, while compounds 6 and 16 (100 μg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time interval of 15 and 30 min. Compounds 1, 12–13, and 15 showed moderate activity. Among the tested hits, compounds 5 (17.3 ± 2.2), 11 (16.2 ± 2.1), and 8 (16.1 ± 2.1) showed significant anti-nociceptive potential. Molecular docking studies on the most active anti-nociceptive hits indicated that the activity might be attributed to the ability of the compounds to target μ-opioid receptor (μOR) effectively. Furthermore, compounds 14 and 11 showed anti-bacterial activity against Pseudomonas aeruginosa and MSRA with MIC of 40.97 and 54.77 μg/mL, respectively. In addition, the predicted ADMET profile of 5, 9, and 11 indicates that these molecules follow the drug-likeness criteria, and their activity can be enhanced through structural optimization.

Grayanane diterpenoids from Craibiodendron yunnanense with anti-inflammatory and antinociceptive activities

Twenty-five grayanane diterpenoids including six undescribed compounds (craibiodenoside A-F), were isolated from the leaves of Craibiodendron yunnanense W. W. Smith. The structures of the isolated compounds were determined by 1D-NMR, 2D-NMR, and HR-ESI-MS spectrometric analyses. All compounds were evaluated for their anti-inflammatory activities by inhibiting the release of interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells. The results demonstrated that three undescribed compounds craibiodenoside A, B, F, and three known compounds could inhibit the release of IL-6 significantly. In addition, the antinociceptive activities of compounds were assessed using acetic acid-induced writhing test. Craibiodenoside D, grayanoside D, and rhodojaponins VI exhibited notable antinociceptive activities. Specifically, rhodojaponins VI exhibited antinociceptive activity with the inhibition percentage of 87.6%.

Design, Synthesis and Biological Activity of New Amides Derived from 3-Benzhydryl and 3-sec-Butyl-2,5-dioxo-pyrrolidin-1-yl-acetic Acid.

The aim of this study was to design and synthesize two new series of pyrrolidine-2,5-dione-acetamides with a benzhydryl or sec-butyl group at position 3 as potential anticonvulsants. Their anticonvulsant activity was evaluated in standard animal models of epilepsy: the maximal electroshock (MES), the 6 Hz, and the subcutaneous pentylenetetrazole (scPTZ) tests. The in vivo studies revealed the most potent anticonvulsant activity for 15 (3-(sec-butyl)-1-(2-(4-(3-trifluoromethylphenyl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione), with ED50 values of 80.38 mg/kg (MES) and 108.80 mg/kg (6 Hz). The plausible mechanism of action was assessed in in vitro binding assays, in which 15 interacted effectively with voltage-gated sodium (site 2) and L-type calcium channels at a concentration of 100 μM. Subsequently, the antinociceptive activity of compounds 7 and 15 was observed in the hot plate test of acute pain. Moreover, compounds 7, 11 and 15 demonstrated an analgesic effect in the formalin test of tonic pain. The hepatotoxic properties of the most effective compounds (7, 11 and 15) in HepG2 cells were also investigated.

Antinociceptive grayanane-derived diterpenoids from flowers of Rhododendron molle

Twelve new grayanoids (1−12) along with five known compounds were isolated from flowers of Rhododendron molle. Their structures were fully characterized using a combination of spectroscopic analyses, computational calculations, and single crystal X-ray diffraction. Rhomollone A (1) possesses an unprecedented 5/6/6/5 tetra-cyclic ring system (B-nor grayanane) incorporating a cyclopentene-1,3-dione scaffold. Rhodomollein XLIII (2) is a dimeric grayanoid, containing a novel 14-membered heterocyclic ring with a C2 symmetry axis. The antinociceptive activities of compounds 3, 4, 6, 7, and 12−17 were evaluated by an acetic acid-induced writhing test. Among them, compounds 3, 7, 12, 15 and 16 displayed significant antinociceptive activities at a dose of 20 mg/kg with inhibition rates ranging from 41.9% to 91.6%. Compounds 6 and 13 inhibited 46.0% and 39.4% of the acetic acid-induced writhes at a dose of 2 mg/kg, while compound 17 inhibited 34.3% of the writhes at a dose of 0.4 mg/kg.

Antinociceptive Diterpenoids from the Leaves and Twigs of Rhododendron decorum.

Three new leucothane-type (1-3), two new micrathane-type (4, 5), eight new grayanane-type diterpenoids (6-13), and four known compounds were obtained from the ethanol extract of the leaves and twigs of Rhododendron decorum. The structures were determined based on NMR spectra, quantum chemical calculations, and X-ray crystallography. The antinociceptive activities of compounds 1, 3, 4, 6, 8, 10-13, and 15-17 were evaluated via the acetic acid-induced writhing test. Compounds 1, 8, 11-13, and 15 exhibited significant antinociceptive activities. In particular, 12 and 15 were found to be effective at doses of 0.8 and 0.08 mg/kg, respectively.

Antimicrobial, anti-inflammatory, and antinociceptive activities of triazole, pyrazole, oxadiazine, oxadiazole, and sugar hydrazone-5-nitroindoline-2-one derivatives and a study of their computational chemistry ( part II)

Objective The aim of this study (part II) is to evaluate the antibacterial, anti-inflammatory, and antinociceptive activities of a series of 1H-1,2,4-triazol-3-yl)phenylimino)(methylbenzyl)-5-nitroindolin-2-ones, 1H-pyrazole-1-carbonyl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 3-(4-(1,3,4-oxadizine-6-one)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones, 1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-ones and 4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) sugar hydrazone derivatives (1–13) and, in addition, to investigate their computational chemistry. Methods The synthesized compounds in (part I) 1–9 were evaluated for their antibacterial and antifungal activities using different strains of Gram-positive bacteria (Bacillus subtilis), Gram-negative bacteria (Pseudomonas aeruginosa), yeast (Candida albicans), and four mold fungi (Fusarium solani, Aspergillus niger, Colletotrichum gloeosporioides, and Phomopsis obscurans). The anti-inflammatory and antinociceptive activities of compounds 1–13 were evaluated using a hot-plate test, acetic acid-induced writhing in mice, formalin-induced nociception, a tail immersion test, and carrageenan-induced hind paw edema. For computational chemistry, a semiempirical MNDO method (Modified Neglect of Differential Overlap is a semi-empirical method for the quantum calculation of molecular electronic structure in computational chemistry) associated with HyperChem professional 7.5 programs was adapted. Results and conclusion Compounds 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) and 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (9) showed the highest antibacterial and antifungal activities compared with clotrimazole and sulfamethoxazole as reference drugs. In contrast, compounds ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), 3-(4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-carbonyl) phenylimino)-1-(p-methylbenzyl)-5-nitroindolin-2-one (8), D-glucose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (10), and D-arabinose-4-(-1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino) hydrazone derivative (12) showed significantly high anti-inflammatory and antinociceptive activities when compared with indomethacin and morphine as reference drugs. From the computational chemistry compounds, ethyl 4-(5-nitro-2-oxoindolin-3-ylideneamino) benzoate (1), ethyl 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzoate (2), and 4-[(1-(p-methylbenzyl)-5-nitro-2-oxoindolin-3-ylideneamino)] benzohydrazide (3) yielded the lowest values of total energy and heat of formation, and had higher stability than other molecules.

Anti-inflammatory and anti-nociceptive activities of compounds from Tinospora sagittata (Oliv.) Gagnep.

Radix Tinosporae is a herb widely used in traditional Chinese medicine for the treatment of various inflammatory diseases. In the present study, its anti-inflammatory and antinociceptive activities were investigated. The ethanol extract of Radix Tinosporae exhibited significant inhibitory effects on xylene-induced ear edema and acetic acid-induced writhing in mice. Using bioassay-guided fractionation, the n-butanol fraction was determined as the active fraction. Further purification of the most active n-butanol fraction led to the isolation of three compounds, palmatine, columbamine and columbinyl glucoside. All three compounds showed inhibitory activities on xylene-induced ear edema, but only palmatine and columbamine exhibited significant inhibitory effects on acetic acid-induced writhing. In addition, palmatine and columbamine markedly inhibited in vitro production of nitric oxide and nuclear factor-kappaB activation in RAW264.7 macrophage cells in response to lipopolysaccharide or tumor necrosis factor alpha stimulation. These results provide justification for the utilization of Radix Tinosporae in Chinese folk medicine for the treatment of inflammatory diseases.