An approach to QSAR of 16-substituted pregnenolones as microsomal enzyme inducers

Rekka, Eleni A.; Kourounakis, Panos N.

doi:10.1007/bf03190271

Cited by 6 publications

(2 citation statements)

References 8 publications

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“…Apigenin can control dose dependant dermal inflammation (Gerritsen et al, 1995), and prevent drug, stress and alcohol dependent gastric ulcer (Szelenyi et al, 1979). In vitro studies have shown that MC oil extract has antioxidant activities (Rekka and Kourounakis, 1996). Main mechanism of extracts and essences in controlling the lipids oxidative stress and peroxidation is not well understood, but it is possible they act in starting stage of none stratified fatty acids (Chevalier et al, 1999;Joseph et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive effect of Matricaria chamomilla on vincristine-induced peripheral neuropathy in mice

Nouri¹

2012

Afr. J. Pharm. Pharmacol.

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Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus, effective therapeutic strategy is required. In this study, the antinociceptive effect of Matricaria chamomilla (MC) hydroalcoholic extract and morphine on vincristine-induced peripheral neuropathy model in mice has been investigated. Experiments were performed on 60 Naval Medical Research Institute (NMRI) male mice. Mouse subsequently received daily intraperitoneal and intravenal injections of vincristine sulfate, saline and MC hydroalcoholic extract over 12 days, immediately following behavioral testing. For assessment of pain, formalin test was preformed. The effects of MC, morphine and vehicle (saline) 30 min before formalin test on vincristine-induced neuropathy were evaluated. Administration of MC before formalin injection showed significant (P < 0.05) decrease of pain responses in both phases. Administration of vincristine produced significant (Pm < 0.05) increase in pain response in second phase of formalin test. Injection of MC and vincristine together has shown that MC is able to decrease the vincristine induced pain significantly (P < 0.05). Morphine decreased vincristine induced pain test significantly (P < 0.05). In comparison, morphine has analgesic effects in the first phase and MC has anti-inflammatory effects in the second phase of formalin test significantly (P < 0.05). These results suggest that MC may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Antinociceptive effect of Matricaria chamomilla on vincristine-induced peripheral neuropathy in mice

Nouri¹

2012

Afr. J. Pharm. Pharmacol.

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“…In summary, the steroid skeleton can initiate docking to the receptor site, probably through lipophilic interactions; the interaction is completed by a favorable electronic effect at the 16α-position. Regarding the stereochemistry of the 16-substituent, the orientation of the group, but not the bulk, seems to be of importance for a successful and, thus, productive fit [ 64 ].…”

Section: Structure-activity Relationshipsmentioning

confidence: 99%

Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind

et al. 2017

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Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems) and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes. A number of mechanisms are presented. Structure-activity studies are also discussed. Vitamin E, as well as two synthetic novel compounds, seem to reduce both oxidative and biological stress and, consequently, influence drug response and metabolism.

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Ekins¹,

Boulanger

Swaan

et al. 2002

Journal of Computer-Aided Molecular Design

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With the continual pressure to ensure follow-up molecules to billion dollar blockbuster drugs, there is a hurdle in profitability and growth for pharmaceutical companies in the next decades. With each success and failure we increasingly appreciate that a key to the success of synthesized molecules through the research and development process is the possession of drug-like properties. These properties include an adequate bioactivity as well as adequate solubility, an ability to cross critical membranes (intestinal and sometimes blood-brain barrier), reasonable metabolic stability and of course safety in humans. Dependent on the therapeutic area being investigated it might also be desirable to avoid certain enzymes or transporters to circumvent potential drug-drug interactions. It may also be important to limit the induction of these same proteins that can result in further toxicities. We have clearly moved the assessment of in vitro absorption, distribution, metabolism, excretion and toxicity (ADME/TOX) parameters much earlier in the discovery organization than a decade ago with the inclusion of higher throughput systems. We are also now faced with huge amounts of ADME/TOX data for each molecule that need interpretation and also provide a valuable resource for generating predictive computational models for future drug discovery. The present review aims to show what tools exist today for visualizing and modeling ADME/TOX data, what tools need to be developed, and how both the present and future tools are valuable for virtual filtering using ADME/TOX and bioactivity properties in parallel as a viable addition to present practices.

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An approach to QSAR of 16-substituted pregnenolones as microsomal enzyme inducers

Cited by 6 publications

References 8 publications

Antinociceptive effect of Matricaria chamomilla on vincristine-induced peripheral neuropathy in mice

Antinociceptive effect of Matricaria chamomilla on vincristine-induced peripheral neuropathy in mice

Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind

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