Novel δ 2 -isoxazolines as group II phospholipase A 2 inhibitors

Basappa, Basappa; Kumar, Mohit; Swamy, S. Nanjunda; Mahendra, M.; Prasad, J. Shashidhara; Viswanath, Bannikuppe S.; Rangappa, Kanchugarakoppal S.

doi:10.1016/j.bmcl.2004.05.012

Cited by 34 publications

(13 citation statements)

References 11 publications

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“…With this concern, the current study probed the neutralizing efficacy of apigenin structural analogue (5d) on SVMP-induced pharmacological effects both in pre-incubation as well as independent injection experiments. In a similar study, we previously reported the PLA2 and cholinesterase inhibitory activities of novel isoxazolines and small oxazine compounds as anti-tumor agent [41]–[43].…”

Section: Discussionmentioning

confidence: 56%

Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

et al. 2014

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The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues are synthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC) venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological study further conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and bothropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound 5d could be a potent agent in viper bite management.

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Section: Discussionmentioning

confidence: 56%

Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

et al. 2014

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“…The compound losartan potassium, a non-peptide small molecule bearing biphenyl aromatic group and imidazole, combines an angiotensin II receptor (type AT 1 ) antagonist and diuretic property. In the light of the above observations, the incorporation of the active 1,2,4-triazole nucleus to the biphenyl ring is part of our continued effort towards the synthesis and study of the biological properties of condensed nitrogen and sulphur heterocycles [8][9][10]. We report the synthesis and X-ray crystal structure analysis of a possible bioactive molecule, 2-(4-methyl-2 -biphenyl)-4-amino-1,2,4-triazole-3-thiol (4).…”

Section: Introductionmentioning

confidence: 98%

Synthesis and crystal structure analysis of 2-(4-methyl-2′-biphenyl)-4-amino-1,2,4-triazole-3-thiol

et al. 2006

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The bioactive compound 2-(4-methyl-2 -biphenyl)-4-amino-1,2,4-triazole-3-thiol, F.W. 282.09 was synthesized, characterized by spectroscopic techniques and confirmed by X-ray crystal structure analysis. The title compound crystallizes in monoclinic class under the space group P2 1 /c with cell parameters, a = 11.273(3) Å, b = 17.245(1) Å, c = 7.413(1) Å, β = 97.742(5) • and Z = 4. The structure exhibits inter-molecular hydrogen bonding of the type N-H···S.

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“…As a part of continued efforts toward incorporation of the active 1,2,4-triazole nucleus to the biphenyl ring for the purpose of the synthesis and study of the biological properties of condensed nitrogen and sulfur-containing heterocycles [56][57][58] Swamy et al [59] studied the synthesis and characterization of the bioactive compound 2-(4-methyl-2 0 -biphenyl)-4-amino-1,2,4-triazole-3-thiol using spectroscopic techniques and X-ray crystal structure analysis. The compound crystallizes in monoclinic class under the space group P2 1 /c and exhibits inter-molecular hydrogen bonding of the type N-HÁÁÁS.…”

Section: Issuementioning

confidence: 99%