Synthesis and Evaluation of Antimicrobial and Anticonvulsant Activities of Some New 3-[2-(5-Aryl-1,3,4-oxadiazol-2-yl/4-Carbethoxymethylthiazol-2-yl)imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and Investigation of Their Structure-Activity Relationships

Altintas, Handan; Ateş, Öznur; Uydeş-Doğan, B. Sönmez; İlkay, F. Alp; Kaleli, Deniz; Özdemir, Osman; Birteksöz, Seher; Ötük, Gülten; Şatana, Dilek; Uzun, Meltem

doi:10.1055/s-0031-1296716

Cited by 3 publications

(2 citation statements)

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“…In addition, 20 mg/kg dose of HHL-6 was potent enough to retard the slow progression of seizure score when compared to PTZ-control group resulting in significant protective effect of HHL-6 on the development of kindling process. These observations were in accordance for the previous studies involving the compounds having tryptamine derivatives or indole rings in their structures [ 30 – 32 ]. Since PTZ most likely produces seizures by inhibiting GABA neurotransmission [ 33 , 34 ] specifically acting as GABA A receptor antagonist, the drugs preventing convulsions and seizures in PTZ-treated mice or increasing the latency to seizures may work either by enhancing GABA activity or antagonizing glutamate neurotransmission.…”

Section: Discussionsupporting

confidence: 93%

Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6

Malhi

Jawed

Hanif

et al. 2014

BioMed Research International

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Brain-derived neurotrophic factor (BDNF) and c-Fos are shown to promote epileptogenesis and are taken as a marker of neuronal activity. The present study investigated the expression of BDNF and c-Fos in mice brain with pentylenetetrazol- (PTZ-) induced generalized seizure and evaluated the effect of novel tryptamine derivative HHL-6 on the expression of these two markers. The subconvulsive dose of PTZ (50 mg/kg) was administered on alternate days in the experimental groups until the seizure scores 4-5 developed in the PTZ-control group. At the end of each experiment, animals were sacrificed, brain samples were collected and cryosectioned, and immunohistochemical analysis of BDNF and c-Fos protein was performed. Data obtained from two sections per mouse (n = 12 animals/group) is presented as means ± S.E.M. The test compound HHL-6 demonstrated a potent anticonvulsant activity in the PTZ-induced seizure in mice. Significant reduction in the BDNF (P < 0.003) and c-Fos (P < 0.01) protein expression was observed in the HHL-6 treated group. Based on these results we suggest that one of the possible mechanisms of HHL-6 to inhibit epileptogenesis might be due to its controlling effect on the cellular and molecular expression of the factors that contribute to the development of epileptogenic plasticity in the CNS.

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Section: Discussionsupporting

confidence: 93%

Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6

Malhi

Jawed

Hanif

et al. 2014

BioMed Research International

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“…Such particular ring (thiazolidin-4-one) was selected, in part, because of its involvement in molecules that have been reported previously as anticonvulsant agents [46][47][48][49][50][51][52][53][54][55][56] ; additionally, being of a similar size and containing atoms that might participate in hydrogen bonding like the parent thiosemicarbazone. 45) Different substituents at position 3 and position 5 in the thiazolidine-4-one nucleus were introduced to study their effect on the anticonvulsant activity.…”

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confidence: 99%

Synthesis and Anticonvulsant Activity of Certain Substituted Furochromone, Benzofuran and Flavone Derivatives

et al. 2010

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Despite the optimal use of the currently available antiepileptic drugs, 30 to 40% of the epileptic population fails to experience seizure control, and others do so only at the expense of significant toxic effects that range in severity from minimal brain impairment to death from aplastic anemia or hepatic failure.1-3) These facts provoked the need for new anticonvulsant drugs with higher potency and fewer side effects. Several studies reported that chromone derivatives are promising anticonvulsant candidates that perform their activity through a g-aminobutyric acid (GABA)-mediated mechanism. [4][5][6][7][8][9][10][11][12][13][14][15][16][17] Likewise, flavones (2-phenylbenzopyrons) are with a well known positive GABA-modulating ability; their central activity was attributed to their potential to penetrate the blood-brain barrier which is strongly correlated to their lipophilicity.18) Semicarbazones and their bioisosteres thiosemicarbazones, have a documented essential role in the design of novel anticonvulsant agents that performing their anticonvulsant activity also through a GABA-mediated mechanism.19-41) Extensive structure-activity relationship studies proposed certain pharmacophoric requirements for (thio)-semicarbazones interaction at the binding site which are a hydrophobic binding area represented by aryl or heteroaryl group and a hydrogen bonding domain represented by the NH-CO(S)-NH system. [24][25][26]33,38) It was suggested that (thio)semicarbazones anticonvulsant activity is mediated through GABA-mediated mechanism. 19,22,29,32,37,41) In the present investigation the two anticonvulsant candidates, chromones or flavones and thiosemicarbazones, were amalgamated to obtain more potent anticonvulsants compounds of series 1 and 2. In the synthesized hybrid compounds the chromone or the furochromone ring acts as the hydrophobic aryl ring required for binding which itself possesses anticonvulsant tendency. On the other hand, various bicyclic heterocycles containing thiosemicarbazono group showed significant anticonvulsant activity. 33,34,[42][43][44] Herein the tricyclic furochromone moiety was simplified to the bicyclic benzofuran system, which was reported to possess anticonvulsant activity [42][43][44] to give compounds of series 3. Obviously, the compounds of this series are the bicyclic analogs of the reported phenyl congener 4 synthesized by Dimmock et al. which showed marked anticonvulsant activity. 20) Replacement of the phenyl ring in 4 by the bicyclic benzofuran structure is thought to increase the hydrophobic aryl area which binds to the binding site and thus may enhance the binding. Moreover, the effect of the hydrophobic group on the terminal amino group of the thiosemicarbazono moiety was studied in the synthesized compounds of series 1, 2 and 3.Due to certain limitations associated with the (thio)semicarbazone functionality, mainly the poor solubility and liability to metabolism 45) ; improvement of the molecule, pharmacologically and pharmaceutically, was carried out by replacement of the th...

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Investigation of Antimicrobial Activities of Indole-3-Aldehyde Hydrazide/Hydrazone Derivatives

Gurkok¹,

Altanlar

Süzen³

2008

Chemotherapy

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Background: Indoles and hydrazone-type compounds constitute an important class of compounds for new drug development in order to discover an effective compound against multi-drug-resistant microbial infections. Methods: A series of indole-3-aldehyde and 5-bromoindole-3-aldehyde hydrazide and hydrazones was evaluated for their in vitro antimicrobial activities using the 2-fold serial dilution technique against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, Bacillus subtilis and Candida albicans. The minimum inhibitory concentration (MIC) was determined for test compounds and for the reference standards sultamicillin, ampicillin, fluconazole and ciprofloxacin. Results: Compounds possessed a broad spectrum of activity having MIC values of 6.25–100 mg/ml against the tested microorganisms. Compounds 1a–1j, in particular, displayed better activity against MSRA and significant activity against S. aureus relative to ampicillin. Unexpectedly, indole nicotinic acid hydrazides showed no significant activity while indole anisic acid hydrazides displayed better activity. Conclusion: The results may be instructive to researchers attempting to gain more understanding of the antimicrobial activity of indole hydrazide/hydrazone-type compounds.

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Synthesis and Evaluation of Antimicrobial and Anticonvulsant Activities of Some New 3-[2-(5-Aryl-1,3,4-oxadiazol-2-yl/4-Carbethoxymethylthiazol-2-yl)imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and Investigation of Their Structure-Activity Relationships

Cited by 3 publications

References 15 publications

Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6

Modulation of c-Fos and BDNF Protein Expression in Pentylenetetrazole-Kindled Mice following the Treatment with Novel Antiepileptic Compound HHL-6

Synthesis and Anticonvulsant Activity of Certain Substituted Furochromone, Benzofuran and Flavone Derivatives

Investigation of Antimicrobial Activities of Indole-3-Aldehyde Hydrazide/Hydrazone Derivatives

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