Synthesis and Biological Evaluation of Polyfluoroalkylated Antipyrines and their Isomeric O-Methylpyrazoles

Background: Formally belonging to the non-steroidal anti-inflammatory drug class pyrazolones have long been used in medical practices. Objective: Our goal is to synthesize N-methylated 1-aryl-3-polyfluoroalkylpyrazolones as fluorinated analogs of antipyrine, their isomeric O-methylated derivatives resembling celecoxib structure and evaluate biological activities of obtained compounds. Methods: In vitro (permeability) and in vivo (anti-inflammatory and analgesic activities, acute toxicity, hyperalgesia, antipyretic activity, “open field” test) experiments. To suggest the mechanism of biological activity, molecular docking of the synthesized compounds was carried out into the tyrosine site of COX-1/2. Conclusion: The trifluoromethyl antipyrine represents a valuable starting point in design of the lead series for discovery new antipyretic analgesics with anti-inflammatory properties.

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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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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 ◽

Synthesis And Biological Evaluation

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.

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Anti-Inflammatory and Antinociceptive Activity of Pollen Extract Collected by Stingless Bee Melipona fasciculata

International Journal of Molecular Sciences ◽

10.3390/ijms20184512 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4512 ◽

Cited By ~ 8

Author(s):

Alberto Jorge Oliveira Lopes ◽

Cleydlenne Costa Vasconcelos ◽

Francisco Assis Nascimento Pereira ◽

Rosa Helena Moraes Silva ◽

Pedro Felipe dos Santos Queiroz ◽

...

Keyword(s):

Native Species ◽

Biological Activities ◽

Stingless Bee ◽

In Vitro Assays ◽

Pollen Extract ◽

Biological Potential ◽

Anti Inflammatory ◽

Analgesic Activities

The stingless bee, Melipona fasciculata Smith (Apidae, Meliponini), is a native species from Brazil. Their products have high biotechnological potential, however there are no studies about the biological activities of pollen collected by M. fasciculata. In this context, the present study investigated the chemical composition, anti-oxidant, anti-inflammatory, and analgesic activities of hydroethanolic pollen extracts collected by M. fasciculata in three cities in Maranhão State, Brazil. We verified the antioxidant activity of the extracts and inhibitory activity against the cyclooxygenase enzyme using in vitro assays and in allowed to select the extract with higher efficiency to be used on in vivo assays. In these trials, the selected extract showed high anti-inflammatory activity as well as nociceptive effects at central and peripheral level, suggesting that this extract acts on inhibition of histamine release and decreased synthesis of prostaglandins and the in-silico study suggested that polyphenols and acids fatty acids in the extract may be associated with these activities. The results of the present study report the high biological potential of pollen extract and we conclude that the pollen collected by M. fasciculata can be considered as the object of research for new pharmacological alternatives.

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Design, Synthesis and Pharmacological Evaluation of Gastro- Protective Anti-inflammatory Analgesic Agents based on Dual Oxidative Stress / Cyclooxygenase Inhibition

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523018666190325155244 ◽

2020 ◽

Vol 19 (3) ◽

pp. 268-290 ◽

Cited By ~ 1

Author(s):

Monika Gaba ◽

Sarbjot Singh ◽

Chander Mohan ◽

Richa Dhingra ◽

Monika Chauhan ◽

...

Keyword(s):

Antioxidant Activity ◽

Inhibitory Activity ◽

Frap Assay ◽

Anti Oxidant ◽

Cox 2 ◽

Anti Inflammatory ◽

Analgesic Activities ◽

Cox 1

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) derived local generation of reactive oxygen species (ROS) plays a crucial role in the formation of gastric ulceration. Objective: Therefore, anti-inflammatory analgesics with potent antioxidant activity could be a potential therapeutic strategy for the treatment of pain and inflammatory disorders without gastrointestinal (GI) side effects. Methods: In an effort to develop gastroprotective analgesic and anti-inflammatory agents, a series of 2-methylamino-substituted-1H-benzo[d] imidazol-1-yl) (phenyl) methanone derivatives were synthesized and evaluated in vitro for cyclooxygenase (COX) inhibition as well as anti-oxidant potential by the FRAP assay. The compounds with significant in vitro COX-1/COX-2 inhibitory activity and antioxidant activity were further screened in vivo for their anti-inflammatory and analgesic activities. Moreover, the ulcerogenic potential of test compounds was also studied. To gain insight into the plausible mode of interaction of compounds within the active sites of COX-1 and COX-2, molecular docking simulations were performed. Results: Among the various synthesized molecules, most of the compounds showed good cyclooxygenase inhibitory activity and efficient antioxidant activity in FRAP assay. After preliminary and indicative in vitro assays, three compounds exhibited most significant antiinflammatory and analgesic activity with better gastric tolerability during their in vivo evaluation. Ligand interaction studies indicated highest dock score -43.05 of 1,2- disubstituted benzimidazole derivatives in comparison to the reference ligand -30.70. Overall studies provided us (2-((4-methoxyphenylamino) methyl) -1h-benzo [d] imidazol- 1-yl) (phenyl) methanone as a lead with potent gastro-protective anti-inflammatory and analgesic activities that can be used for future research. Conclusion: From the above results, it can be concluded that designing of multifunctional molecules with COX-1/COX-2 inhibitory and anti-oxidant activities could hold a great promise for further development of GI-safer NSAIDs.

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Synthesis and biological evaluation of myricetin-pentadienone hybrids as potential anti-inflammatory agents in vitro and in vivo

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.103597 ◽

2020 ◽

Vol 96 ◽

pp. 103597

Author(s):

Chao Liu ◽

Xu Han ◽

Pei Jing Yu ◽

Liu Zeng Chen ◽

Wei Xue ◽

...

Keyword(s):

Biological Evaluation ◽

Anti Inflammatory ◽

Synthesis And Biological Evaluation

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Hybrid Design of Isonicotinic Acid Hydrazide Derivatives: Machine Learning Studies, Synthesis and Biological Evaluation of their Antituberculosis Activity

Current Drug Discovery Technologies ◽

10.2174/1570163816666190411110331 ◽

2020 ◽

Vol 17 (3) ◽

pp. 365-375

Author(s):

Vasyl Kovalishyn ◽

Diana Hodyna ◽

Vitaliy O. Sinenko ◽

Volodymyr Blagodatny ◽

Ivan Semenyuta ◽

...

Keyword(s):

Machine Learning ◽

Isonicotinic Acid ◽

Acid Hydrazide ◽

Predictive Ability ◽

Antitubercular Activity ◽

Biological Evaluation ◽

Starting Point ◽

Binary Classifiers ◽

Synthesis And Biological Evaluation

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs. Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Methods: The On-line Chemical Database and Modeling Environment (OCHEM) was used to build predictive machine learning models. Seven compounds were synthesized and tested in vitro for their antitubercular activity against H37Rv and resistant Mtb strains. Results: A set of predictive models was built with OCHEM based on a set of previously synthesized isoniazid (INH) derivatives containing a thiazole core and tested against Mtb. The predictive ability of the models was tested by a 5-fold cross-validation, and resulted in balanced accuracies (BA) of 61–78% for the binary classifiers. Test set validation showed that the models could be instrumental in predicting anti- TB activity with a reasonable accuracy (with BA = 67–79 %) within the applicability domain. Seven designed compounds were synthesized and demonstrated activity against both the H37Rv and multidrugresistant (MDR) Mtb strains resistant to rifampicin and isoniazid. According to the acute toxicity evaluation in Daphnia magna neonates, six compounds were classified as moderately toxic (LD50 in the range of 10−100 mg/L) and one as practically harmless (LD50 in the range of 100−1000 mg/L). Conclusion: The newly identified compounds may represent a starting point for further development of therapies against Mtb. The developed models are available online at OCHEM http://ochem.eu/article/11 1066 and can be used to virtually screen for potential compounds with anti-TB activity.

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Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178617999201106113114 ◽

2020 ◽

Vol 17 ◽

Author(s):

Deepak Kumar Singh ◽

Mayank Kulshreshtha ◽

Yogesh Kumar ◽

Pooja A Chawla ◽

Akash Ved ◽

...

Keyword(s):

Molecular Docking ◽

Biological Activities ◽

Inflammatory Activity ◽

Standard Drug ◽

Docking Score ◽

Chemical Structures ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

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Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G

Molecules ◽

10.3390/molecules26113224 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3224

Author(s):

Leander Geske ◽

Ulrich Kauhl ◽

Mohamed E. M. Saeed ◽

Anja Schüffler ◽

Eckhard Thines ◽

...

Keyword(s):

Total Synthesis ◽

Biological Activities ◽

Biological Evaluation ◽

Aromatic Substitution ◽

Substitution Reactions ◽

Total Syntheses ◽

Wittig Olefination ◽

Starting Point ◽

Perkin Reaction ◽

Synthesis And Biological Evaluation

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

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Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Pharmaceutics ◽

10.3390/pharmaceutics13070991 ◽

2021 ◽

Vol 13 (7) ◽

pp. 991

Author(s):

Melanie S. Matos ◽

José D. Anastácio ◽

Cláudia Nunes dos Santos

Keyword(s):

Biological Activities ◽

Sesquiterpene Lactones ◽

Physiological State ◽

Plant Secondary Metabolites ◽

Inflammatory Pathways ◽

Inflammatory State ◽

Anti Inflammatory ◽

Inflammatory Molecules

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure–activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.

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