Design, synthesis, characterization, and biological evaluation of pyrido[1,2-a]pyrimidinone coumarins as promising anti-inflammatory agents

Madar, Jyoti M.; Shastri, Lokesh A.; Holiyachi, Megharaja; Naik, Nirmala S.; Kulkarni, Rashmi C.; Shaikh, Farzanabi; Sungar, Vinay A.

doi:10.1080/00397911.2017.1397698

Cited by 17 publications

(11 citation statements)

References 21 publications

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“…Pain and inflammation often arise due to bacterial infections [24]. Inflammation is nothing but a biological process that arises due to physical, chemical, biological and immunological stimuli to the human body [25], for that, inflammation is the significant indication in numerous pathological conditions such as Alzheimer's disease, osteoarthritis, rheumatoid arthritis and obesity-related diseases [26,27].…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

Synthesis of Biologically Active Molecules through Multicomponent Reactions

et al. 2020

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Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also, highlights the fact that many of such molecules are biologically active or at least have been submitted to any biological screen. The selected papers covered in this review must meet two mandatory requirements: (1) the reported products should be obtained via a multicomponent reaction; (2) the reported products should be biologically actives or at least tested for any biological property. Given the diversity of synthetic approaches utilized in MCRs, the highly diverse nature of the biological activities evaluated for the synthesized compounds, and considering their huge structural variability, much of the reported data are organized into concise schemes and tables to facilitate comparison, and to underscore the key points of this review.Molecules 2020, 25, 505 2 of 71 acetylcholinesterase inhibitors, anti-HIV, antimicrobial, antioxidant, anti-mycobacterial and anticancer activities ( Figure 1). It is noteworthy that 64% and 16% of the supporting literature found for this review correspond to heterocyclic structures with anticancer and antimicrobial activities, respectively. Scheme 2. Three-component synthesis of 3,4-dihydropyrimidinones/thiones type 7 under microwave irradiation, for anti-inflammatory activity.Patil et al., reported a one-pot pseudo-five-component synthesis of highly functionalized tetrahydropyridines 9 using Cu(OTf) 2 as catalyst, Scheme 3. In vitro anti-inflammatory activity of the obtained compounds 9 was determined against matrix metalloproteinases (MMPs) as MMP-2 and MMP-9 by using gelatin zymography [29]. Scheme 3. Multicomponent Cu(OTf) 2 catalyzed synthesis of substituted tetrahydropyridines 9 for anti-inflammatory activity.A highly diastereoselective synthesis (exclusively the cis isomer is formed), of chromeno β-lactam hybrids 13/14 was also achieved by an efficient one-pot three-component reaction between either 5,5-dimethylcyclohexane-1,3-dione (10a) or 4-hydroxycoumarin (10b), diverse benzaldehydes 11 and malononitrile (12), in the presence of DABCO under reflux conditions (Scheme 4). Scheme 4. Three-component synthesis of β-lactam hybrids 13/14 for anti-inflammatory activity.The synthesized compounds (13 in 80-95% yield) and (14 in 82-95% yield) were screened for anti-inflammatory activity (as well as for anticancer activity, please see Section 3.13.13. Compound 13b (Ar = 4-ClC 6 H 4 , Ar 1 = 4-MeC 6 H 4 ) was the most active of all the chromeno β-lactam hybrids 13/14 tested, with a 19.8 anti-inflammatory ratio, although, it resulted less active than the reference drug dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation [30].

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Section: Anti-inflammatory Activitymentioning

confidence: 99%

Synthesis of Biologically Active Molecules through Multicomponent Reactions

et al. 2020

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“…The fused coumarin–pyrimidinone hybrids also demonstrated certain antibacterial activity, [ 108,109 ] and hybrids 49a – c (MIC: 1.0–4.0 µg/ml) were comparable to cefixime (MIC: 2.0 µg/ml) against S. aureus , B. subtilis , E. coli , and P. aeruginosa , so they are attractive scaffolds for the development of novel antibacterial agents.…”

Section: Coumarin–pyrimidine Hybridsmentioning

confidence: 99%

Coumarin‐containing hybrids and their antibacterial activities

Feng

Zhang

Yang

et al. 2020

Archiv der Pharmazie

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Infections caused by Gram-positive and -negative bacteria are one of the foremost causes of morbidity and mortality globally. Antibiotics are the mainstay of therapy for bacterial infections, but the emergence and wide spread of drug-resistant pathogens have already become a huge issue for public healthcare systems. The coumarin moiety, which is ubiquitous in nature, could bind to the B subunit of DNA gyrase in bacteria and inhibit DNA supercoiling by blocking the ATPase activity; hence, coumarin derivatives possess potential antibacterial activity. Several coumarin-containing hybrids such as coumermycin A1, clorobiocin, and novobiocin have already been used in clinical practice for the treatment of various bacterial infections; thus, it is conceivable that hybridization of the coumarin moiety with other antibacterial pharmacophores may provide opportunities for the development of novel antibiotics. This review outlines the advances in coumarin-containing hybrids with antibacterial potential in the recent 5 years and the structure-activity relationships are also discussed. K E Y W O R D S antibacterial, coumarin, hybrid compounds, structure-activity relationships

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“…Inflammation is an indication of many pathological conditions, such as rheumatoid arthritis, osteoarthritis, Alzheimer's disease, hepatitis, cancer, pulmonary fibrosis and obesity-related diseases [11,12]. Lipopolysaccharide (LPS), a bacterial endotoxin, plays an important role during inflammation by regulating a cascade of cellular responses [13].…”

Section: Introductionmentioning

confidence: 99%

One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents

et al. 2020

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Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for their antioxidant, α-amylase enzyme inhibitory, anti-proliferative and anti-inflammatory activities. SF8 showed the lowest IC50 of 29.19 ± 0.25 µg/mL by scavenging DPPH free radicals. SF5 showed significant antioxidant activity in total antioxidant capacity (TAC) and total reducing power (TRP) assays. SF5 and SF9 showed the maximum inhibition of α-amylase enzyme i.e., 97.47% and 89.93%, respectively, at 200 µg/mL concentration. Five compounds were shortlisted to determine their anti-proliferative potential against Hep-2C cells. The study was conducted for 24, 48 and 72 h. SF8 showed significant results, having an IC50 value of 11.9 ± 1.04 µM at 72 h when compared with standard cisplatin (IC50 value of 14.6 ± 1.01 µM). An in vitro nitric oxide (NO) assay was performed to select compounds for in vivo anti-inflammatory activity evaluation. SF13 scavenged the NO level to a maximum of 85% at 50 µM concentration, followed by SF1 and SF2. Based on the NO scavenging assay results, in vivo anti-inflammatory studies were also performed and the results showed significant activity compared to the standard, acetylsalicylic acid (ASA).

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Design, synthesis, characterization, and biological evaluation of pyrido[1,2-a]pyrimidinone coumarins as promising anti-inflammatory agents

Cited by 17 publications

References 21 publications

Synthesis of Biologically Active Molecules through Multicomponent Reactions

Synthesis of Biologically Active Molecules through Multicomponent Reactions

Coumarin‐containing hybrids and their antibacterial activities

One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents

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