Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach

Bosquesi, Priscila Longhin; Melo, Tais Regina Ferreira; Vizioli, Ednir de Oliveira; Santos, Jean Leandro dos; Chin, Chung Man

doi:10.3390/ph4111450

Cited by 76 publications

(37 citation statements)

References 61 publications

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“…Alpha-Lipoic acid (α-LA, ALA) is a compound which is found in many prokaryotic and eukaryotic cell types and is formed naturally (1). α-LAhaspositive effectsonsomatic and autonomic neuropathies in diabetes, normalizes the endoneural blood flow, lowers oxidative stress and improves vascular dysfunction (2).…”

mentioning

confidence: 99%

Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

Turamanlar¹,

Özen²,

Songür³

et al. 2015

Balkan Med J

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Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250-300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were no statistically significant changes in NO. Conclusion: Increased fibronectin observed after ischemia/reperfusion of rat sciatic nerve is reduced after the administration of ALA. This indicates that the function of fibronectin, to reconnect cut nerve segments and regenerate nerves, is more prominent than its function in tissue healing after ischemia. ALA administered before ischemia decreases MDA and increases SOD and GSHPx. We think that ALA may protect against the pathological changes in ischemic nerve and may be used to devise more efficient treatments. Keywords: Alpha lipoic acid, ischemia-reperfusion, sciatic nerve, rat

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mentioning

confidence: 99%

Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

Turamanlar¹,

Özen²,

Songür³

et al. 2015

Balkan Med J

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“…The development of new anti-inflammatory drugs via hybridization techniques through linking of new entities or mutual prodrugs has been used extensively in literature to obtain new compounds with better actions [7]. It is reported that a promising anti-inflammatory compounds were synthesized by condensation of salicylic acid carbohydrazide with substituted Isatin (Figure 8) [28].…”

Section: Discussionmentioning

confidence: 99%

“…In order to attain that goal, many approaches were used including hybridization techniques through linking of new entities or mutual prodrugs [7]. …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

Ibrahim

Elsaman

Al-Nour

2018

International Journal of Medicinal Chemistry

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The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Diclofenac Schiff's bases (M1, M2, M4, M7, and M8) were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, 1H NMR, 13C NMR, and MS). The compounds were synthesized via Schiff's condensation reaction and their anti-inflammatory activity was investigated applying the Carrageenan-induced paw edema model against Diclofenac as positive control. Percentage inhibition of edema indicated that all compounds were exhibiting a comparable anti-inflammatory activity as Diclofenac. Moreover, the anti-inflammatory activity was supported via virtual screening using molecular docking study. Interestingly compound M2 showed the highest in vivo activity (61.32% inhibition) when compared to standard Diclofenac (51.36% inhibition) as well as the best binding energy score (-10.765) and the virtual screening docking score (-12.142).

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“…If a toxicophore fragment of a given drug molecule does not overlap the pharmacophore, then it may be possible to redesign the molecule (32). For example, thalidomide derivatives devoid of teratogenic effects have been developed for treating chronic inflammation employing hybridization techniques, based on studies demonstrating that the teratogenicity is due to its distinct toxic subunit, glutarimide (33). PQ, an 8-aminoquinoline, has serious side effects and is known to induce hemolysis, especially in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals.…”

Section: Advantages Of Hybridsmentioning

confidence: 99%

Are Antimalarial Hybrid Molecules a Close Reality or a Distant Dream?

Agarwal

Gupta

Awasthi

2017

Antimicrob Agents Chemother

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Emergence of drug-resistant Plasmodium falciparum strains has led to a situation of haste in the scientific and pharmaceutical communities. Hence, all their efforts are redirected toward finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. In light of this situation, scientists have come up with the concept of hybridization of two or more active pharmacophores into a single chemical entity, resulting in "antimalarial hybrids." The approach has been applied widely for generation of lead compounds against deadly diseases such as cancer and AIDS, with a proven potential for use as novel drugs, but is comparatively new in the sphere of antimalarial drug discovery. A sudden surge has been evidenced in the number of studies on the design and synthesis of hybrids for treating malaria and may be regarded as proof of their potential advantages over artemisinin-based combination therapy (ACT). However, it is evident from recent studies that most of the potential advantages of antimalarial hybrids, such as lower toxicity, better pharmacokinetics, and easier formulation, have yet to be realized. A number of questions left unaddressed at present need to be answered before this approach can progress to the late stages of clinical development and prove their worth in the clinic. To the best of our knowledge, this compilation is the first attempt to shed light on the shortcomings that are surfacing as more and more studies on molecular hybridization of the active pharmacophores of known antimalarials are being published.

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Anti-Inflammatory Drug Design Using a Molecular Hybridization Approach

Cited by 76 publications

References 61 publications

Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

Synthesis, Anti-Inflammatory Activity, and In Silico Study of Novel Diclofenac and Isatin Conjugates

Are Antimalarial Hybrid Molecules a Close Reality or a Distant Dream?

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