Abstract 3306: Screening potential drug candidates for treatment of glioblastoma patients utilizing an in-vivo mouse/ rat model system

Background: Since the first isolation of antimicrobial peptides (AMPs) they have attracted extensive interest in medicinal chemistry. However, only a few AMP-based drugs are currently available on the market. Despite their effectiveness, biodegradability, and versatile mode of action that is less likely to induce resistance compared to conventional antibiotics, AMPs suffer from major issues that need to be addressed to broaden their use. Notably, AMPs can lack selectivity leading to side effects and cytotoxicity, and also exhibit in vivo instability. Several strategies are being actively considered to overcome the limitations that restrain the success of AMPs. Methods: In the current work, recent strategies reported for improving AMPs in the context of drug design and delivery were surveyed, and also their possible impact on patients and the environment was assessed. Results: As a major advantage AMPs possess an easily tunable skeleton offering opportunities to improve their properties. Strategic structural modifications and the beneficial properties of cyclic or branched AMPs in term of stability have been reported. The conjugation of AMPs with nanoparticles has also been explored to increase their in vivo stability. Other techniques such as the coupling of AMPs with specific antibodies aim to increase the selectivity of the potential drug towards the target. These strategies were evaluated for their effect on the environment highlighting green technologies. Conclusion: Although further research is needed taking into account both environmental and human health consequences of novel AMPs, several of these compounds are promising drug candidates for use in sustainable medicine.

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Medicinal Utility of Some Schiff Bases and their Complexes with First Transition Series Metals: A Review

Oriental Journal Of Chemistry ◽

10.13005/ojc/370506 ◽

2021 ◽

Vol 37 (5) ◽

pp. 1051-1061

Author(s):

Tahmeena Khan ◽

Saima Zehra ◽

Almas Alvi ◽

Umama Fatima ◽

Alfred J. Lawrence

Keyword(s):

Transition Metal ◽

Metal Complexes ◽

Transition Metal Complexes ◽

Present Review ◽

Potential Drug ◽

Drug Candidates ◽

Transition Series ◽

Low Toxicity ◽

Activity Enhancement

Schiff based ligands and their complexes have emerged as potential drug candidates. Owing to their excellent chelating tendency, they easily coordinate with transition metals which have vacant orbitals. Transition metal complexes have several advantages because of their better acceptability and low toxicity in biological systems. These metals also serve as micronutrients and as co-factors of various metallo-enzymes which justifies the need of their designing and synthesis. Many modifications have been suggested in the ligand moiety for the purpose of activity enhancement and some of them have been described in the present review. These modifications have enhanced better potency against a number of diseases and resulting in low toxicity and better solubility in vivo. The transition metal complexes with Schiff based complexes have exhibited an array of activities including anticancer, antioxidant and antimicrobial. Their analytical applications have also been reported. The present review summarizes some of the recent advances in the field of synthesis and designing of new Schiff based complexes particularly with first transition series metals and their medicinal applications.

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63 In-vitro and in-vivo evaluation of HCV polymerase inhibitors as potential drug candidates for treatment of chronic hepatitis C infection

Journal of Hepatology ◽

10.1016/s0168-8278(04)90063-3 ◽

2004 ◽

Vol 40 ◽

pp. 23

Author(s):

S. Dagan ◽

E. Ilan ◽

S. Aviel ◽

O. Nussbaum ◽

E. Arazi ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Potential Drug ◽

Hepatitis C Infection ◽

In Vivo Evaluation ◽

Drug Candidates ◽

Polymerase Inhibitors

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Computational screening for potential drug candidates against the SARS-CoV-2 main protease

F1000Research ◽

10.12688/f1000research.23829.1 ◽

2020 ◽

Vol 9 ◽

pp. 514 ◽

Cited By ~ 2

Author(s):

Bruno Silva Andrade ◽

Preetam Ghosh ◽

Debmalya Barh ◽

Sandeep Tiwari ◽

Raner José Santana Silva ◽

...

Keyword(s):

Natural Compounds ◽

Potential Drug ◽

Drug Candidates ◽

Positive Effects ◽

Computational Screening ◽

Main Protease ◽

Zinc Database ◽

Structural Assembly

Background: SARS-CoV-2 is the causal agent of the current coronavirus disease 2019 (COVID-19) pandemic. They are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly, and pathogenicity. The approximately 33.8 kDa Mpro protease of SARS-CoV-2 is a non-human homologue and is highly conserved among several coronaviruses, indicating that Mpro could be a potential drug target for Coronaviruses. Methods: Herein, we performed computational ligand screening of four pharmacophores (OEW, remdesivir, hydroxychloroquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7), and also screened 50,000 natural compounds from the ZINC Database dataset against this protease target. Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 11 best selected ligands, namely ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as beta-carboline, alkaloids, and polyflavonoids, and all displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as other known ligands. Conclusions: Our results suggest that these 11 molecules could be effective against SARS-CoV-2 protease and may be subsequently tested in vitro and in vivo to develop novel drugs against this virus.

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T CELL-CONTROL OF TUMOR CELLS IN VIVO IN A RAT MODEL SYSTEM OF ATL.

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology ◽

10.1097/00042560-199904010-00041 ◽

1999 ◽

Vol 20 (4) ◽

pp. A12

Author(s):

M. Kannagi ◽

T. Ohashi ◽

S. Hanabuchi ◽

Y. Koya ◽

H. Kato ◽

...

Keyword(s):

T Cell ◽

Tumor Cells ◽

Rat Model ◽

Model System ◽

Cell Control

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Evaluation of the neuroprotective activity of a new allylmorpholine derivative in a rat model of traumatic brain injury

Drug development & registration ◽

10.33380/2305-2066-2021-10-4(1)-179-187 ◽

2021 ◽

Vol 10 (4) ◽

pp. 179-187

Author(s):

V. A. Prikhodko ◽

A. V. Kan ◽

Yu. I. Sysoev ◽

I. A. Titovich ◽

N. A. Anisimova ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Rat Model ◽

Neurological Deficit ◽

Elevated Plus Maze ◽

Neuroprotective Activity ◽

Drug Candidates ◽

Plus Maze

Introduction. The search for and development of new drugs capable of reducing the severity of neurological deficit in traumatic brain injury are a critical task for investigational pharmacology. Chromone-containing allylmorpholines are a new group of neuroprotective drug candidates that have been shown to inhibit acetylcholinesterase and butyrylcholinesterase, and block N-methyl-D-aspartate receptors in vitro.Aim. This study aimed to evaluate the neuroprotective activity of the allylmorpholine derivative (E)-4-[3-(8-bromo-6-methyl-4-oxo-4H-chromen- 3-yl)-1-cyclohexylallyl]morpholin-4-ium chloride (33b) in vivo using a rat model of traumatic brain injury.Materials and methods. Traumatic brain injury was induced using the controlled cortical impact model. The allylmorpholine derivative was administered intraperitoneally at 1, 10, or 50 mg × kg-1 b.w. at 1 h after trauma induction, and then daily for the next 6 d. The neurological deficit was assessed using the Limb Placing, Open Field, Elevated Plus Maze, Beam Walking, and Cylinder tests.Results and discussion. At all doses administered, the allylmorpholine derivative had no positive effect on the motor function or exploratory behavior following traumatic brain injury. In the Elevated Plus Maze, 10 mg × kg-1 b.w. of the compound further suppressed exploratory behaviour in the injured animals, which appears to be consistent with its sedative properties observed previously in zebrafish.Conclusion. Despite the previously described in vitro affinity of allylmorpholines towards several molecular targets crucial for the pathogenesis of brain trauma and posttraumatic functional recovery, an allylmorpholine derivative had no neuroprotective effect in a rat model of traumatic brain injury in this study. These results further emphasize the importance of in vivo evaluation of potential neuroprotective drug candidates.

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Computer-Aided Prediction and Identification of Phytochemicals as Potential Drug Candidates against MERS-CoV

BioMed Research International ◽

10.1155/2021/5578689 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Hafiza Salaha Mahrosh ◽

Muhammad Tanveer ◽

Rawaba Arif ◽

Ghulam Mustafa

Keyword(s):

Respiratory Infections ◽

Catalytic Triad ◽

World Health ◽

In Vivo Studies ◽

Pharmacokinetic Parameters ◽

Potential Drug ◽

Drug Candidates ◽

Starting Point ◽

Computer Aided

The Middle East respiratory syndrome coronavirus (MERS-CoV) is the major leading cause of respiratory infections listed as blueprint of diseases by the World Health Organization. It needs immediate research in the developing countries including Saudi Arabia, South Korea, and China. Still no vaccine has been developed against MERS-CoV; therefore, an effective strategy is required to overcome the devastating outcomes of MERS. Computer-aided drug design is the effective method to find out potency of natural phytochemicals as inhibitors of MERS-CoV. In the current study, the molecular docking approach was employed to target receptor binding of CoV. A total of 150 phytochemicals were docked as ligands in this study and found that some of the phytochemicals successfully inhibited the catalytic triad of MERS-CoV. The docking results brought novel scaffolds which showed strong ligand interactions with Arg178, Arg339, His311, His230, Lys146, and Arg139 residues of the viral domains. From the top ten ligands found in this study (i.e., rosavin, betaxanthin, quercetin, citromitin, pluviatilol, digitogenin, ichangin, methyl deacetylnomilinate, kobusinol A, and cyclocalamin) based on best S -score values, two phytochemicals (i.e., pluviatilol and kobusinol A) exhibited all drug-likeness properties following the pharmacokinetic parameters which are important for bioavailability of drug-like compounds, and hence, they can serve as potential drug candidates to stop the viral load. The study revealed that these phytochemicals would serve as strong potential inhibitors and a starting point for the development of vaccines and proteases against MERS-CoV. Further, in vivo studies are needed to confirm the efficacy of these potential drug candidates.

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Computational Screening for Potential Drug Candidates Against SARS-CoV-2 Main Protease

10.20944/preprints202004.0003.v2 ◽

2020 ◽

Cited By ~ 1

Author(s):

Bruno Andrade ◽

Preetam Ghosh ◽

Debmalya Barth ◽

Sandeep Tiwari ◽

Raner José Santana Silva ◽

...

Keyword(s):

Potential Drug ◽

Drug Candidates ◽

Positive Effects ◽

Computational Screening ◽

Main Protease ◽

Zinc Database ◽

Novel Drugs ◽

Structural Assembly

Background: SARS-CoV-2 that are the causal agent of a current pandemic are enveloped, positive-sense, single-stranded RNA viruses of the Coronaviridae family. Proteases of SARS-CoV-2 are necessary for viral replication, structural assembly and pathogenicity. The ~33.8KDa Mpro protease of SARS-CoV-2 is a non-human homologue and highly conserved among several coronaviruses indicating Mpro could be a potential drug target for Coronaviruses.Methods: Here we performed computational ligand screening of four pharmacophores (OEW, Remdesivir, Hydroxycholoquine and N3) that are presumed to have positive effects against SARS-CoV-2 Mpro protease (6LU7) and also screened 50,000 molecules from the ZINC Database dataset against this protease target.Results: We found 40 pharmacophore-like structures of natural compounds from diverse chemical classes that exhibited better affinity of docking as compared to the known ligands. The 10 best selected ligands namely, ZINC1845382, ZINC1875405, ZINC2092396, ZINC2104424, ZINC44018332, ZINC2101723, ZINC2094526, ZINC2094304, ZINC2104482, ZINC3984030, and ZINC1531664, are mainly classified as β-carboline, Alkaloids and Polyflavonoids, and all of them displayed interactions with dyad CYS145 and HIS41 from the protease pocket in a similar way as with other known ligands.Conclusion: Our results suggest that these 10 molecules could be effective against SARS-CoV-2 protease and may be tested in vitro and in vivo to develop novel drugs against this virus.

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