Design, Synthesis and Biological Evaluation of Some 2‐<scp>A</scp>zetidinone Derivatives as Potential Antihyperlipidemic Agents

Arya, Nikhilesh; Dwivedi, Jaya; Khedkar, Vijay M.; Coutinho, Evans C.; Jain, Kishor S.

doi:10.1002/ardp.201300262

Cited by 14 publications

(7 citation statements)

References 26 publications

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“…Significant antihyperlipidemic activity in some of the synthetic compounds especially 27 was observed, which is comparable to the standard drug, ezetimibe [125].…”

Section: New Synthetic Cholesterol Absorption Inhibitorsmentioning

confidence: 80%

Discovery Approaches for Novel Dyslipidemia Drugs

Maqbool¹,

Safavi²,

Bahadar³

et al. 2015

CDDT

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Statins are, currently available, best choice of drugs for treating dyslipidemia and coronary diseases. In addition to this, lipid lowering drugs support treatment to a great extent, either as monotherapy or in combinations with other groups. Pravastatin used in combination with cholesteryl ester, transfers protein inhibitors (CETP) to produce efficient results. Peroxisome proliferator-activated receptor agonists (PPAR) like muraglitazar, aleglitazar and tesaglitazar are PPAR α/γ receptor agonist, dual in action performs better in phase 3 clinical study and reduces renal and cardiovascular events. By targeting both receptors, a better treatment for cardiovascular and diabetic problems can be achieved. Proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors like humanized monoclonal antibodies, are newly discovered inhibitors that reduce the risk of cardiovascular diseases. During the past few years, nucleic acid-based therapies targeting lipid and lipoprotein metabolism, such as microsomal TG transfer protein (MTP) may be a promising therapeutic approach to treat vascular diseases. Gene regulating transcription factors involved in bile acids and cholesterol metabolism can be controlled by FXR agonists in dyslipidemia. To overcome these drawbacks, many thyroid hormone analogues have been developed to lower down cholesterol level by targeting specifically thyroid hormone β receptors abundantly present in the liver without severe side effects. Virtual screening, an important tool in screening databases of the lead compounds, provides a good platform to access new compounds. In this review, examples of novel FXR modulators, thyromimetic agents, cholesterol absorption inhibitors and other new anti hyperlipidemia scaffolds have been addressed.

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“…Significant antihyperlipidemic activity in some of the synthetic compounds especially 27 was observed, which is comparable to the standard drug, ezetimibe [125].…”

Section: New Synthetic Cholesterol Absorption Inhibitorsmentioning

confidence: 80%

Discovery Approaches for Novel Dyslipidemia Drugs

Maqbool¹,

Safavi²,

Bahadar³

et al. 2015

CDDT

View full text Add to dashboard Cite

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“…Further, these triazole derivatives ( 5 ) refluxed with substituted aldehydes in acidic medium to afford benzylidine derivatives 6 ( a – j ) . The benzylidine derivatives reacted with chloroacetyl chloride and in the presence of triethylamine as base to afford azitidine derivatives 7 ( a – j ) .…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of Some Phenyl Substituted Azetidine Containing 1, 2, 4‐triazole Derivatives as Antibacterial Agents

Dhall

Jain

Mishra

et al. 2018

Journal of Heterocyclic Chem

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A novel series of phenyl substituted azetidine containing 1, 2, 4‐triazole derivatives 7(a–j) were synthesized and characterized by IR, 1HNMR, 13CNMR, and mass spectroscopy. Synthesized 1, 2, 4‐triazole derivatives were subsequently assayed in vitro to investigate their antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli using broth dilution method. Compounds 7c, 7d, and 7e exhibited potent inhibitory activities as compared to standard cefotaxime. Further, fluorescence spectral studies were also carried out to ascertain the antibacterial potential of compound 7c against two bacterial strains, that is, P. aeruginosa and S. aureus. In docking studies, all the compounds exhibited good docking scores between −12.04 and −11.36 kcal/mol and indicated that compounds could act through inhibition of bacterial DNA gyrase (PDB ID 3U2D). Among all, 7c has shown the maximum docking score and found in agreement to in vitro studies. In conclusion, synthesized 1, 2, 4‐triazole derivatives holds substantial caliber to be categorized as antibacterial agents.

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“…In case of NPC1L1, eventhough, the its crystal structure with ligand N -acetylglucosamine complexed with it was available (PDB ID: 3QNT) (Kwon et al 2011 ), we considered ezetimibe, a known cholesterol lowering drug acting on this target as a reference ligand in the present study for a better comparison (Arya et al 2013 ).…”

Section: Computational Detailsmentioning

confidence: 99%

Docking study of novel antihyperlipidemic thieno[2,3-d]pyrimidine; LM-1554, with some molecular targets related to hyperlipidemia - an investigation into its mechanism of action

et al. 2014

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An investigation into the mechanism of antihyperlipidemic action of 2-chloromethyl-5,6,7,8-tetrahydrobenzo(b)thieno[2,3-d]pyrimidin-4(3H)-one (LM-1554) was carried out through docking experiments with six different molecular targets; Niemann Pick C1 Like1 protein (NPC1L1), ATP citrate lyase (ACL), C-reactive protein (CRP), lanosterol 14α-demethylase (LDM), squalene synthase (SqS) and farnesiod X-receptor (FXR) known to be implicated in the physiology of hyperlipidemia. The interactions of LM-1554 were compared with the interactions of their respective co-crystallized native ligands at the active sites of these receptors. These comparisons are based on their docking parameters, as well as, types of interactions and vicinity with various amino acids in the active site pockets. The interaction of LM-1554 with the target, NPC1L1 has been found to be the quite favourable as compared to those with the other targets assessed in this study.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-628) contains supplementary material, which is available to authorized users.

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Design, Synthesis and Biological Evaluation of Some 2‐Azetidinone Derivatives as Potential Antihyperlipidemic Agents

Cited by 14 publications

References 26 publications

Discovery Approaches for Novel Dyslipidemia Drugs

Discovery Approaches for Novel Dyslipidemia Drugs

Synthesis and Evaluation of Some Phenyl Substituted Azetidine Containing 1, 2, 4‐triazole Derivatives as Antibacterial Agents

Docking study of novel antihyperlipidemic thieno[2,3-d]pyrimidine; LM-1554, with some molecular targets related to hyperlipidemia - an investigation into its mechanism of action

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