The in vitro and in vivo study of oleanolic acid indole derivatives as novel anti-inflammatory agents: synthesis, biological evaluation, and mechanistic analysis

Purpose: The work was performed to investigate the feasibility of preparing ocular inserts loaded with Poly-ε-Caprolactone (PCL) nanoparticles as a sustained ocular delivery system. Methods: First, Atorvastatin Calcium-Poly-ε-Caprolactone (ATC-PCL) nanoparticles were prepared and characterized. Then, the optimized nanoparticles were loaded within inserts formulated with Methylcellulose (MC) and Polyvinyl Alcohol (PVA) by a solvent casting technique and evaluated physically, for in-vitro drug release profile. Finally, an in-vivo study was performed on the selected formulation to prove non-irritability and sustained ocular anti-inflammatory efficacy compared with free drug-loaded ocuserts. Results: The results revealed (ATC-PCL) nanoparticles prepared with 0.5% pluronic F127 were optimized with 181.72±3.6 nm particle size, 0.12±0.02 (PDI) analysis, -27.4± 0.69 mV zeta potential and 62.41%±4.7% entrapment efficiency. Nanoparticles loaded ocuserts manifested compatibility between drug and formulation polymers. Moreover, formulations complied with average weight 0.055±0.002 to 0.143±0.023 mg, and accepted pH. ATC-PCL nanoparticles loaded inserts prepared by 5% MC showed more sustained, prolonged in-vitro release over 24h. In-vivo study emphasized non-irritability, ocular anti-inflammatory effectiveness represented by smaller lid closure scores, and statistically significant lowering in PMN count after 3h. Conclusion: These findings proposed a possibly simple, new and affordable price technique to prepare promising (ATC-PCL) nanoparticles loaded inserts to achieve sustained release with prolonged antiinflammatory efficacy.

Oleanolic acid indole derivatives as novel α-glucosidase inhibitors: Synthesis, biological evaluation, and mechanistic analysis

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104580 ◽

2021 ◽

Vol 107 ◽

pp. 104580

Author(s):

Panpan Wu ◽

Hao He ◽

Hang Ma ◽

Borong Tu ◽

Jiahao Li ◽

...

Keyword(s):

Oleanolic Acid ◽

Biological Evaluation ◽

Indole Derivatives ◽

Glucosidase Inhibitors ◽

Mechanistic Analysis

Synthesis and biological evaluation of some novel pyrazolopyrimidines incorporating a benzothiazole ring system

Acta Pharmaceutica ◽

10.2478/acph-2013-0001 ◽

2013 ◽

Vol 63 (1) ◽

pp. 19-30 ◽

Cited By ~ 11

Author(s):

Mohammed Afzal Azam ◽

Loganathan Dharanya ◽

Charu Chandrakant Mehta ◽

Sumit Sachdeva

Keyword(s):

Antimicrobial Activity ◽

Diclofenac Sodium ◽

Biological Evaluation ◽

Ring System ◽

Standard Drug ◽

Anti Inflammatory ◽

Pyrimidine Moiety ◽

In the present study, a series of benzothiazol derivatives 3a-l containing pyrazolo[3,4-d]pyrimidine moiety at the second position were synthesized and characterized by analytical and spectral data. The compounds were tested for their in vitro antimicrobial activity. Compounds 1-(1,3-benzothiazol-2- yl)-3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine (3a), 1- (1,3-benzothiazol-2-yl)-4-(4-chlorophenyl)-3-methyl-1H-pyrazolo[ 3,4-d]pyrimidine (3d) and 1-(1,3-benzothiazol-2-yl)- 3-methyl-4-substituted phenyl-1H-pyrazolo[3,4-d]pyrimidines (3h-j) showed significant inhibitory activity against P. aeruginosa whereas compounds 1-(1,3-benzothiazol-2-yl)-4- (2-chlorophenyl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine (3b), 2-[1-(1,3-benzothiazol-2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin- 4-yl]phenol (3e), 1-(1,3-benzothiazol-2-yl)-4-(3,4-dimethoxyphenyl)- 3-methyl-1H-pyrazolo[3,4-d]pyrimidine (3h), 4-[1-(1,3-benzothiazol-2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyri midin-4-yl]-N,N-dimethylaniline (3j) and 1-(1,3-benzothiazol- 2-yl)-3-methyl-4-[2-phenylvinyl]-1H-pyrazolo[3,4-d]pyrimidine (3k) were found to be active against C. albicans. Some of these synthesized compounds were evaluated for their in vivo acute toxicity, analgesic, anti-inflammatory, and ulcerogenic actions. The tested compound 4-[1-(1,3-benzothiazol- 2-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-N, N-dimethylaniline (3j) exhibited maximum analgesic and anti-inflammatory activities. Compounds 1-(1,3-benzothiazol- -2-yl)-3-methyl-4-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidine (3i) and 3j showed a significant gastrointestinal protection compared to the standard drug diclofenac sodium.

Design, Synthesis and Biological Evaluation of Novel 1, 3, 4-Oxadiazole Bearing Pyridine Moiety

International Journal of Scientific Research in Science and Technology ◽

10.32628/ijsrst196535 ◽

2019 ◽

pp. 300-307

Author(s):

Asma D. Ambekari ◽

Shrinivas K. Mohite

Keyword(s):

Antimicrobial Activity ◽

Mass Spectra ◽

Biological Evaluation ◽

Design Synthesis ◽

Pyridine Moiety ◽

Anti Inflammatory ◽

Physicochemical Data ◽

Series of novel substituted Synthesis of N-{[5-(substituted)-1,3,4-oxadiazole-2-yl] carbamothioyl} derivatives containing 1,3,4-oxadiazole moiety were synthesized by microwave as a green chemistry method and conventional method by using pyridine 3- carboxylic acid as a starting material. The structures of the synthesized compounds were characterized by physicochemical data, IR, Mass spectra and 1HNMR. All the newly synthesized compound screened for their antimicrobial and In-vivo and In-vitro Anti-inflammatory studies. Anti-inflammatory studies revealed that compound 4f showed significant in-vivo and in-vitro anti-inflammatory activity as well potent antimicrobial activity.

Novel Ester and Acid Derivatives of the 1,5-Diarylpyrrole Scaffold as Anti-Inflammatory and Analgesic Agents. Synthesis and in Vitro and in Vivo Biological Evaluation

Journal of Medicinal Chemistry ◽

10.1021/jm901269y ◽

2010 ◽

Vol 53 (2) ◽

pp. 723-733 ◽

Cited By ~ 33

Author(s):

Mariangela Biava ◽

Giulio C. Porretta ◽

Giovanna Poce ◽

Claudio Battilocchio ◽

Fabrizio Manetti ◽

...

Keyword(s):

Biological Evaluation ◽

Analgesic Agents ◽

Anti Inflammatory ◽

Derivatives Of

Anti-Inflammatory effects of Tetrahydrocurcumin and calcium mineral crystalline: in vitro and in vivo study

Journal of Clinical & Experimental Dermatology Research ◽

10.4172/2155-9554-c2-072 ◽

2018 ◽

Vol 09 ◽

Author(s):

Si Jun Park

Keyword(s):

In Vivo Study ◽

Anti-inflammatory and anticoagulant effects of polyphenol-rich extracts from Thymus atlanticus: An in vitro and in vivo study

Journal of Ethnopharmacology ◽

10.1016/j.jep.2019.112475 ◽

2020 ◽

Vol 252 ◽

pp. 112475 ◽

Cited By ~ 4

Author(s):

Tarik Khouya ◽

Mhamed Ramchoun ◽

Souliman Amrani ◽

Hicham Harnafi ◽

Mustapha Rouis ◽

...

Keyword(s):

In Vivo Study ◽

Effects of Berries on High-Fat Diet-Induced Inflammation

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_082 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 449-449

Author(s):

Patricia Perez ◽

Desiree Wanders ◽

Hannah Land ◽

Kathryn Chiang ◽

Rami Najjar ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Inflammatory Markers ◽

In Vitro Study ◽

Vitro Study ◽

In Vivo Study ◽

High Fat ◽

Abstract Objectives Studies suggest that inflammation mediates the link between obesity and its comorbidities including type 2 diabetes and cardiovascular disease. Hence, there is a demand for effective alternative or complementary approaches to treat obesity-associated inflammation. The objective of this study was to determine whether consumption of blackberries (BL) and raspberries (RB) alone or in combination reduce obesity-induced inflammation. Methods In Vitro Study: RAW 264.7 macrophages were pretreated with either BL, RB, or BL + RB, each at a final concentration of 200 µg/mL for 2 h. LPS (1 ng/mL) was then added to the media for 16 h. mRNA expression of inflammatory cytokines was measured. In Vivo Study: Five-week-old mice were acclimated to a low-fat low-sucrose (LFLS) diet for one week after which mice were randomized 10 per group to one of five groups: 1) LFLS, 2) high-fat high-sucrose (HFHS), 3) HFHS + 10% BL, 4) HFHS + 10% RB, or 5) HFHS + 5% BL + 5% RB. Expression of inflammatory markers was measured in the liver as well as epididymal and inguinal white adipose tissue. Results In Vitro Study: Each berry alone and in combination suppressed the LPS-induced increase in inflammatory markers, with the combination (BL + RB) having the greatest effect. The combination suppressed LPS-induced expression of Ccl2, Tnfa, F4/80, and Il6 by 3.7−, 5.3−, 5.3−, and 4.4-fold, respectively. In Vivo Study: Gene expression analysis indicated that berry consumption had no significant effect on proinflammatory (Ccl2, Il1b, Tnfa, Il6, Itgam) or anti-inflammatory (Adipoq, Arg1, Mgl1) markers in adipose tissue depots or liver. However, relatively low gene expression of inflammatory markers in the tissues indicates that the mice fed the HFHS diet failed to develop a robust inflammatory state. Conclusions BL and RB have direct anti-inflammatory effects on immune cells. Initial analysis indicates that consumption of BL and RB has no significant effects on markers of inflammation in a diet-induced mouse model of obesity. However, it is possible that the relatively low levels of inflammation in these mice masked the anti-inflammatory potential of BL and RB. Ongoing analysis will provide additional insights into the effects of BL and RB on inflammation in these tissues. Funding Sources Lewis Foundation Award.

Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities

10.21203/rs.2.17036/v3 ◽

2020 ◽

Author(s):

Ahmed Shaker ◽

Eman K. A. Abdelall ◽

Khaled R. A. Abdellatif ◽

Hamdy M. Abdel-Rahman

Keyword(s):

Active Site ◽

High Selectivity ◽

Biological Evaluation ◽

Indole Derivatives ◽

E Coli ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors ◽

Abstract Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were evaluated for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA , E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii , respectively with safe therapeutic dose. Compounds 7a-k, 8a-c and 9a-c showed good anti-inflammatory activity with high selectivity toward COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site correlated with results of in vitro COX-2 inhibition assays.

Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl) indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities

10.21203/rs.2.17036/v1 ◽

2019 ◽

Author(s):

Ahmed Shaker ◽

Eman K. A. Abdelall ◽

Khaled R. A. Abdellatif ◽

Hamdy M. Abdel-Rahman

Keyword(s):

Active Site ◽

High Selectivity ◽

Biological Evaluation ◽

Indole Derivatives ◽

E Coli ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 2 Inhibitors ◽

Abstract Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were evaluated for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA , E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii , respectively with safe therapeutic dose. Compounds 7a-k, 8a-c and 9a-c showed good anti-inflammatory activity with high selectivity toward COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site correlated with results of in vitro COX-2 inhibition assays.