Synthesis of Highly Potent Anti-Inflammatory Compounds (ROS Inhibitors) from Isonicotinic Acid

In search of anti-inflammatory compounds, novel scaffolds containing isonicotinoyl motif were synthesized via an efficient strategy. The compounds were screened for their in vitro anti-inflammatory activity. Remarkably high activities were observed for isonicotinates 5–6 and 8a–8b. The compound 5 exhibits an exceptional IC50 value (1.42 ± 0.1 µg/mL) with 95.9% inhibition at 25 µg/mL, which is eight folds better than the standard drug ibuprofen (11.2 ± 1.9 µg/mL). To gain an insight into the mode of action of anti-inflammatory compounds, molecular docking studies were also performed. Decisively, further development and fine tuning of these isonicotinates based scaffolds for the treatment of various aberrations is still a wide-open field of research.

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Construction of a novel quinoxaline as a new class of Nrf2 activator

10.21203/rs.2.12921/v1 ◽

2019 ◽

Author(s):

Murugesh Kandasamy ◽

Kit-Kay Mak ◽

Thangaraj Devadoss ◽

Punniyakoti Veeraveedu Thanikachalam ◽

Raghavendra Sakirolla ◽

...

Keyword(s):

Docking Studies ◽

Metabolic Stability ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

New Class ◽

Ic50 Value ◽

Kelch Domain ◽

Anti Inflammatory ◽

Nrf2 Activator

Abstract The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation provides cytoprotection against numerous inflammatory disorders. N-nicotinoylquinoxaline-2-carbohdyrazide (NQC) was designed by combining the important pharmacophoric features of bioactive compounds reported in the literature. NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using LPSEc induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using ELISA. The Nrf2 activity of the compound NQC was determined using ‘Keap1:Nrf2 Inhibitor Screening Assay Kit’. To obtain the insights on NQC’s activity on Nrf2, molecular docking studies were performed using Schrodinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes. NQC was found to be non-toxic until the dose of 50 µM on RAW 264.7 cells. The NQC showed potent anti-inflammatory effect in an in vitro model of Lipopolysaccharide (LPS) stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. The NQC dose-dependently down regulated the pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α) and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values 13.27 ± 2.37, 10.13 ± 0.58, 14.41 ± 1.83 and 15.23 ± 0.91 µM respectively. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 59.78 ± 6.73, 52.93 ± 7.81, 28.43 ± 8.13 minutes; microsomal intrinsic clearance values; 22.1 ± 4.31, 26.0 ± 5.17 and 47.13 ± 6.34 µL/min/mg protein; respectively. So, rat has comparable metabolic profile with human, thus, rat could be used for predicting the pharmacokinetics and metabolism of NQC in human. NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

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Screening and Application of Chitin Synthase Inhibitors

Processes ◽

10.3390/pr8091029 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1029

Author(s):

Xiaozai Shi ◽

Shuo Qiu ◽

Yingling Bao ◽

Hanchi Chen ◽

Yuele Lu ◽

...

Keyword(s):

Antifungal Activity ◽

Inhibitory Concentration ◽

Inhibitory Effect ◽

Chitin Synthase ◽

Fungal Cell ◽

Ic50 Value ◽

Further Development ◽

Fungicide Target ◽

Better Than

Chitin is an important part of the fungal cell wall, but is not found in plants and mammals, so chitin synthase (CHS) can be a green fungicide target. In this paper, 35 maleimide compounds were designed and synthesized as CHS inhibitors. All the screened compounds showed different degrees of CHS inhibitory activity and antifungal activity in vitro. In particular, the half–inhibitory concentration (IC50) value of compound 20 on CHS was 0.12 mM, and the inhibitory effect was better than that of the control polyoxin B (IC50 = 0.19 mM). At the same time, this compound also showed good antifungal activity and has further development value.

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POTENTIAL ANTIOXIDANT, ANTI-INFLAMMATORY AND ANTIBACTERIAL EVALUATION OF EXTRACTS OF LEUCAS ASPERA USING IN VITRO MODELS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2016v8i11.13711 ◽

2016 ◽

Vol 8 (12) ◽

pp. 292 ◽

Cited By ~ 3

Author(s):

Tahareen S. ◽

Shwetha R. ◽

Myrene R. D.

Keyword(s):

Inflammatory Activity ◽

Total Phenolic ◽

Scavenging Activity ◽

Membrane Stabilization ◽

Standard Drug ◽

Leucas Aspera ◽

Ic50 Value ◽

Anti Inflammatory ◽

Stabilization Assay

Objective: To evaluate the potential antioxidant, anti-inflammatory and antibacterial activities of aqueous and methanolic extracts of leaves of Leucas aspera (Thumbae).Methods: Phytochemical screening of the leaves of L. aspera was followed by analysis of antioxidant activity by means of DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging activity. In vitro anti‐inflammatory activity was evaluated using lipoxygenase inhibition, albumin denaturation assay, membrane stabilization assay and proteinase inhibitory activity at different concentrations. Aspirin was used as a standard drug for the study of anti‐inflammatory activity. Linear regression analysis was used to calculate half maximal inhibitory concentration, IC50 value. The zone of inhibition was performed against common pathogens to determine the antimicrobial activity at different concentrations of plant extracts (60%, 70%, 80%).Results: The phytochemical analysis revealed the presence of carbohydrates, amino acid, alkaloids, tannins, flavonoids, glycosides, xanthoproteins, and phenols. The total phenolic and flavonoid content was found to be 2.25±0.04 mg GAE/g (gallic acid equivalents) and 1.2±0.05 mg QE/g (Quercetin equivalents) of fresh weight tissue respectively. The IC50 values for hydrogen peroxide scavenging activity were found to be 244.6 µg/ml. The extract inhibited the lipoxygenase enzyme activity with an IC50 value of 356.3 µg/ml. Maximum inhibition of heat-induced protein denaturation of 69% was observed at 400 μg/ml, IC50 249.6 μg/ml. Proteinase activity was also significantly inhibited (IC50 = 421.6 μg/ml). Membrane stabilization assay attributed minor protection by the leaf extract with an IC50 of 206.7. It was observed that E. coli were inhibited at all concentrations, followed by Klebsiella and Pseudomonas.Conclusion: Results indicate that L. aspera possess anti-inflammatory properties due to the strong occurrence of polyphenolic compounds such as alkaloids, flavonoids, tannins and steroids that serve as free radical inhibitors or scavenger. Compounds of the plant L. aspera may hence be used as lead compounds for designing potent anti-inflammatory drug which can be used for treatment of various diseases.

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A GREEN AND FACILE APPROACH FOR ANTIDIABETIC AND ANTI-INFLAMMATORY POTENCY FOR FICUS SUBINCISA FRUIT

INDIAN DRUGS ◽

10.53879/id.58.08.12588 ◽

2021 ◽

Vol 58 (08) ◽

pp. 68-74

Author(s):

Abha Shukla ◽

Priyanka Pokhriyal ◽

Rishi K. Shukla ◽

Amanpreet Kaur ◽

Keyword(s):

Ethyl Lactate ◽

Antidiabetic Activity ◽

Green Solvents ◽

Standard Drug ◽

Diet Induced Obesity ◽

Ic50 Value ◽

Health Promoting ◽

Anti Inflammatory ◽

Alcohol Ethyl

Ficus subincisa belongs to the Moraceae family comprising approximately 850 species. Many Ficus species have been used ethnopharmacologically for the treatment of many health-promoting effects. With increasing economical and ecological concerns for several chemical processes, green chemistry is providing various kinds of “green” solvents that can be a recruit for the extraction and isolation of numerous alleviative and important phytoconstituents from plants. The present study was undertaken to prepare crude extracts of F. subincisa fruits with different polarities of green solvents (d-limonene, isopropyl alcohol, ethyl lactate, and hydroalcohol) by using a modified magnetic stirrer extraction method and assessing in vitro anti-diabetic, anti-inflammatory activities by the spectrophotometric method. Among all, ethyl lactate and hydroalcohol fraction of F. subincisa have shown the highest α-amylase and α-glucosidase enzyme inhibitory activity with an IC50 value of 166.91±2.73 and 118.73±0.67 µg/mL, respectively, which were comparable with that of acarbose. At a concentration of 1000 µg/mL, the hydroalcohol and ethyl lactate of fruit produced 134.53±1.23 and 114.67±4.23 µg/mL inhibition of HRBC hemolysis and bovine serum albumin, respectively, as compared with standard drug aspirin and sodium diclofenac. However, there has been no report on the anti-inflammatory and antidiabetic activity of F. subincisa fruit. Therefore this study was aimed to evaluate the anti-inflammatory and antidiabetic activity of F. subincisa fruit extracts of different green solvents. Our study validated the traditional claim with pharmacological data of the Ficus genus. Taken together, these findings imply that the F. subincisa could be useful therapeutic agents to attenuate muscle insulin resistance due to diet-induced obesity and its associated inflammation.

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Molecular Docking Studies, Analgesic and Anti-inflammatory Screening of Some Novel Quinazolin-4-one Derivatives

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23143 ◽

2021 ◽

Vol 33 (5) ◽

pp. 1058-1062

Author(s):

K.N. Rajini Kanth ◽

Ch. Jaswanth Kumar ◽

D. Eswar Tony ◽

Sk. Munwar ◽

Rama Rao Nadendla ◽

...

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Standard Drug ◽

Molecular Docking Studies ◽

Hydrogen Bonding Interactions ◽

Anti Inflammatory ◽

Pharmacological Screening ◽

Analgesic Activities ◽

Cox 2 Inhibitors ◽

Further Development

Molecular docking studies was performed on 20 analogous novel quinazolin-4-one derivatives as cox-2 inhibitors using glide tool of maestro 11.4 application of Schrodinger software. Anti-inflammatory and analgesic activities were further evaluated for the compounds. Based on docking studies, the binding affinity of QZN-16 was found to be -10.32 kcal/mol. In order to understand the significance of R-substituents on the quinazoline-4-one nucleus, the findings of hydrogen bonding interactions between designated ligands with binding site region of 4cox were studied. The ligands which are having high docking score were subjected to pharmacological screening. The compound QZN-16 has shown analgesic and anti-inflammatory activity at a dose level of 50 and 100 mg/kg body weight, respectively when compared with standard drug indomethacin. The newly designed quinazoline-4-one derivatives may serve as lead molecules for further development.

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EVALUATION OF IN VITRO ANTIDIABETIC AND ANTI-INFLAMMATORY ACTIVITIES OF LEAVES EXTRACT OF BOEHMERIA RUGULOSA

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i9.25906 ◽

2018 ◽

Vol 11 (9) ◽

pp. 200

Author(s):

Abha Shukla ◽

Anchal Choudhary

Keyword(s):

Protein Denaturation ◽

Diclofenac Sodium ◽

Significant Inhibition ◽

Inflammatory Activity ◽

Antidiabetic Activity ◽

Standard Drug ◽

Successive Extraction ◽

Ic50 Value ◽

Anti Inflammatory

Objective: The objective of the study is to evaluate in vitro antidiabetic and anti-inflammatory activity of different extracts of leaves of Boehmeria rugulosa by different methods.Methods: In vitro α-glucose and α-amylase were used for antidiabetic activity and lipoxygenase, and protein denaturation method of inhibition assays was used to measure anti-inflammatory activity. Successive extraction of leaves petroleum ether (PE), chloroform (CH), ethyl acetate (EA), acetone (AC), and ethanol (ETH) was performed, and extracts obtained from the extraction were applicable to these activities.Results: The AC extract of leaves shows significantly in vitro antidiabetic activity, and AC has offered significant result 470.07±0.65 μg/mL in the inhibition of α-glucosidase and also for α-amylase assay 698.15±1.71 μg/mL. Acarbose was used as standard. In lipoxidase method, AC had shown better results and in protein denaturation method EA shown the higher inhibition (78.06±0.5 μg/ml) than the other extracts. The standard drug diclofenac sodium also offered significant inhibition against lipoxidase enzyme method with IC50 value 21.76±1.29 μg/mL.Conclusion: These findings suggest that the AC and EA possess potent antidiabetic and anti-inflammatory activities in vitro conditions.

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IN VITRO ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIVITIES OF HINGULESWARA RASABASED HERBOMINERAL FORMULATIONS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11s2.28535 ◽

2018 ◽

Vol 11 (14) ◽

pp. 24

Author(s):

Abhishek Chatterjee ◽

Dileep Singh Baghel ◽

Bimlesh Kumar ◽

Saurabh Singh ◽

Narendra Kumar Pandey ◽

...

Keyword(s):

Antioxidant Activities ◽

Radical Scavenging ◽

Standard Drug ◽

Three Samples ◽

Anti Inflammatory ◽

Dose Dependent ◽

Antioxidant Effects ◽

Made In ◽

In Vitro Antioxidant Activity

Objective: The aims of the present investigation were to develop the herbal and/or herbomineral formulations of Hinguleswara rasa and to compare their anti-inflammatory and antioxidant activities, in vitro, with that of standard drug samples.Methods: This study was an interventional investigation in three samples: In the first sample, Hinguleswara rasa (HR1) was prepared as per methodology described in Rasatarangini using Shuddha Hingula (10 g), Shuddha Vatsanabha (10 g), and Pippali (10 g). In the second and third sample, respectively, Hinguleswara rasa was prepared by replacing Shuddha Hingula with Kajjali where Kajjali made from Hingulotha parada and Sodhita parada constitutes two varieties of Hinguleswara rasa, i.e. HR2 and HR3. In vitro antioxidant activity was studied using 2,2-diphenyl-1-picrylhydrazyl, and the absorbance was recorded at 517 nm. For evaluating the in vitro anti-inflammatory studies, the inhibition of albumin denaturation technique was performed.Results: The results showed that the formulation of Hinguleswara rasa has shown dose-dependent activity which was observed in 100 μg concentration. HR1, HR2, and HR3 showed 36.11, 17.22, and 16.11% radical scavenging activity.Conclusion: It could be concluded that the changes made in the formulations did not affect the in vitro anti-inflammatory and antioxidant effects of the herbomineral formulations.

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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 ◽

Synthesis And Biological Evaluation

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.

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Synthesis and Evaluation of bis-Schiff Bases of Carbohydrazide as Antioxidant and Cytotoxic Agents

Medicinal Chemistry ◽

10.2174/1573406418666211220123403 ◽

2021 ◽

Vol 18 ◽

Author(s):

Sarosh Iqbal ◽

Shumaila Kiran ◽

Shahida Perveen ◽

Rizwana Malik ◽

Muhammad Taha ◽

...

Keyword(s):

Schiff Bases ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Cytotoxic Agents ◽

Scavenging Activity ◽

Standard Drug ◽

Age Related ◽

Dpph Radical Scavenging ◽

Better Than

Background & Introduction : Antioxidants are known to prevent oxidative stress-induced damage to the biomolecules and thus, delay the onset of cancers and many age-related diseases. Therefore, the development of novel and potent antioxidants is justified. Method: During this study, we synthesized symmetrical bis-Schiff bases of carbohydrazide 1-27, and evaluated their in vitro antioxidative activity and cytotoxic activity. Results: Among synthesized compounds, six compounds 20 (IC50 = 12.89 ± 0.02 µM), 16 (IC50 = 14.32 ± 0.43 µM), 17 (IC50 = 18.52 ± 0.83 µM), 19 (IC50 = 22.84 ± 0.62 µM), 24 (IC50 = 35.1 ± 0.82 µM) and 15 (IC50 = 40.03 ± 1.06 µM) showed an excellent 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, better than the standard butylatedhydroxyanisole (BHA) (IC50 = 44.6 ± 0.6 µM). Likewise, two compounds 16 (IC50 = 4.3 ± 1.3 µM) and 20 (IC50 = 6.6 ± 1.6 µM) showed oxidative burst scavenging activity better than the standard drug ibuprofen (IC50 = 11.2 ± 1.9 µM). Some synthesized compounds showed good to moderate toxicity against prostate cancer (PC-3) cell lines. Conclusion: This study has identified potent antioxidants and good cytotoxic agents with the potential to further investigate.

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Design, Synthesis, Characterization, Computational Study and In-vitro Antioxidant and Anti-inflammatory Activities of Few Novel Pyrazol-3-one Derivatives

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i28b31556 ◽

2021 ◽

pp. 220-231

Author(s):

Aziz Unnisa ◽

B. Anupama ◽

Humera Banu ◽

Syeda B. Fatima ◽

K. N. V. Chenchu Lakshmi ◽

...

Keyword(s):

Computational Study ◽

Efficacy And Safety ◽

Dpph Assay ◽

Design Synthesis ◽

Synthetic Compounds ◽

Highly Active ◽

Anti Inflammatory ◽

Further Development ◽

Mutagenic Compound

Aim: To design, synthesize and perform computational study on a few Novel pyrazol-3-one derivatives. Study design: Experimental study. Methodology: A series of 6-aryl substituted pyrimidine azodyes were synthesized by coupling phenyl pyrimidine 2-amine with different aromatic amines. The synthetic compounds were screened for their in-vitro antioxidant and anti-inflammatory activities. The Computational study of designed compounds was done by OCHEM, Molinspiration cheminformatics, Datawarrior, and Swiss ADME. DPPH assay was used to determine the antioxidant activity and heat hemolysis method for anti-inflammatory activity. Results: Molinspiration, Data Warrior, Ochem which are helpful to predict molecule general properties, bioactive scores, toxicity, and drug-likeness. Data Warrior results inferred that the compounds possess moderately active towards mutagenic (compound 2, 11), reproductive (compound 6, 7, 8), and highly active towards Tumorogenic (compound 2) toxicities. OCHEM results showed that most of the synthesized compounds were found to be non-inhibitors of all the subtypes of cytochrome P450 except compound 8. All compounds under this study were effective scavengers of free radicals except the compounds 1, 2, 6, 10. Invitro Anti-inflammatory studies have shown that the compounds (6, 7, 8, 9, 13) active toward heat hemolysis. Conclusion: The synthesized compounds were comprehensively studied and targets were identified rendering them as lead molecules for further development of newer agents with greater efficacy and safety.

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