In vivo analgesic, anti-inflammatory and molecular docking studies of S-naproxen derivatives.

In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.

Oxadiazole Derivatives of Diclofenac as an Anti-proliferative Agent for B-cell Non-Hodgkin Lymphoma: An In vitro and In Silico Studies.

BACKGROUND: Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies. AIM: The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches. METHOD: The compound (II) showed anti-lymphoma activity against both follicular and Burkitt's lymphoma cells, whereas compound (V) inhibited follicular lymphoma cells only. The diclofenac (I) and derivatives (III, IV and VI) exhibited no anti-proliferative effects. The (II) significantly inhibited the expression of BCL-2, p-38 MAPK and TGF-ß in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells (BJ). RESULT: The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in compound (II) is involved in the crucial interactions with the binding site residue. CONCLUSION: The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent.

Evaluation of synthetic aminoquinoline derivatives as urease inhibitors: in vitro, in silico and kinetic studies.

Background: Quinoline and acyl thiourea scaffolds have major chemical significance in medicinal chemistry. Quinoline-based acyl thiourea derivatives may potentially target the urease enzyme. Materials & methods: Quinoline-based acyl thiourea derivatives 1-26 were synthesized and tested for urease inhibitory activity. Results: 19 derivatives (1-19) showed enhanced urease enzyme inhibitory potential (IC50 = 1.19-18.92 µM) compared with standard thiourea (IC50 = 19.53 ± 0.032 µM), whereas compounds 20-26 were inactive. Compounds with OCH3, OC2H5, Br and CH3 on the aryl ring showed significantly greater inhibitory potential than compounds with hydrocarbon chains of varying length. Molecular docking studies were conducted to investigate ligand interactions with the enzyme's active site. Conclusion: The identified hits can serve as potential leads against the drug target urease in advanced studies.

Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives.

Novel ibuprofen derivatives 1-19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2-19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, 1H-, and 13C-NMR spectroscopic techniques. The synthetic molecules 1-19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC50 = 2.96-178 µM as compared to the standard thiourea (IC50 = 21.32 ± 0.22 µM). Out of nineteen, thirteen derivatives 2-4, 6, 7, 9, 11-15, 17, and 18 demonstrated remarkable inhibitory activity with IC50 values of 2.96 ± 1.11 to 16.1 ± 1.07 µM, compound 5 exhibited moderate inhibition with IC50 value of 37.3 ± 0.41 µM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure-activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme.

Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies.

Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α-glucosidase and α-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00-5.6 and 2.04-5.72 µM against α-glucosidase and α-amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B", in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 ±â€¯1.31 µM), (IC50 = 2.5 ±â€¯1.21 µM), 36 (IC50 = 2.12 ±â€¯1.35 µM), (IC50 = 2.21 ±â€¯1.08 µM), and 37 (IC50 = 2.00 ±â€¯1.22 µM), (IC50 = 2.04 ±â€¯1.4 µM) with chloro substitution/s at aryl ring were found to be most active against α-glucosidase and α-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α-amylase and non-competitive mode of inhibition against α-glucosidase enzyme.