A novel crystalline molecular salt of sulfamethoxazole and amantadine hybridizing antiviral-antibacterial dual drugs with optimal in vitro/vivo pharmaceutical properties

The plant of the genus Pterodon (Fabaceae, Leguminosae), commonly known as 'sucupira' or 'faveira', are disseminated throughout the central region of Brazil and has frequently been used in popular medicine for its anti-rheumatic, analgesic, and anti-inflammatory properties. In recent years, interest in these plants has increased considerably. The biological effects of different phytoextracts and pure metabolites have been investigated in several experimental models in vivo and in vitro. The literature describes flavonoids, triterpene and steroids, while one paper presented studies with proteins isolated from the genus. This review provides an overview of phytochemical and pharmacological research in Pterodon, showing the main chemical compounds studied to date, and focusing on the relationship between these molecules and their biological activity. Furthermore, this study paves the way for more in-depth investigation, isolation and characterization of the molecules of this plant genus.

Download Full-text

DOCKING STUDY OF NOVEL N-SUBSTITUTED 2,5-BIS[(7-CHLOROQUINOLIN-4-YL)AMINO]PENTANOIC DERIVATIVES AS SELECTIVE HIGH-BINDER WITH ANGIOTENSIN CONVERTING ENZYME 2

INDIAN DRUGS ◽

10.53879/id.57.08.12425 ◽

2020 ◽

Vol 57 (08) ◽

pp. 16-24

Author(s):

Mohammed Oday Ezzat ◽

Basma M. Abd Razik ◽

Kutayba F. Dawood

Keyword(s):

Angiotensin Converting Enzyme ◽

Active Site ◽

Docking Study ◽

World Health ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Pharmaceutical Properties ◽

Novel Coronavirus

The prevalence of a novel coronavirus (2019-nCoV) in the last few months represents a serious threat as a world health emergency concern. Angiotensin-converting enzyme 2 (ACE2) is the host cellular receptor for the respiratory syndrome of coronavirus epidemic in 2019 (2019-nCoV). In this work, the active site of ACE2 is successfully located by Sitmap prediction tool and validated by different marketed drugs. To design and discover new medical countermeasure drugs, we evaluate a total of 184 molecules of 7-chloro-N-methylquinolin-4-amine derivatives for binding affinity inside the crystal structure of ACE2 located active site. A novel series of N-substituted 2,5-bis[(7-chloroquinolin-4-yl)amino]pentanoic acid derivatives is generated and evaluated for a prospect as a lead compound for (2019-nCoV) medication with a docking score range of (-10.60 to -8.99) kcal/mol for the highest twenty derivatives. Moreover, the ADME pharmaceutical properties were evaluated for further proposed experimental evaluation in vitro or in vivo

Download Full-text

Metabolomics profiling, bio-pharmaceutical properties of Hypericum lanuginosum extracts by in vitro and in silico approaches

Industrial Crops and Products ◽

10.1016/j.indcrop.2019.03.033 ◽

2019 ◽

Vol 133 ◽

pp. 373-382 ◽

Cited By ~ 9

Author(s):

Mohamad Fawzi Mahomoodally ◽

Gokhan Zengin ◽

Dimitrina Zheleva-Dimitrova ◽

Adriano Mollica ◽

Azzurra Stefanucci ◽

...

Keyword(s):

In Silico ◽

Pharmaceutical Properties

Download Full-text

Ethylcellulose in Organic Solution or Aqueous Dispersion Form in Designing Taste-Masked Microparticles by the Spray Drying Technique with a Model Bitter Drug: Rupatadine Fumarate

Polymers ◽

10.3390/polym11030522 ◽

2019 ◽

Vol 11 (3) ◽

pp. 522 ◽

Cited By ~ 2

Author(s):

Katarzyna Wasilewska ◽

Marta Szekalska ◽

Patrycja Ciosek-Skibinska ◽

Joanna Lenik ◽

Anna Basa ◽

...

Keyword(s):

Spray Drying ◽

Electronic Tongue ◽

Aqueous Dispersion ◽

Taste Masking ◽

Organic Solution ◽

Aqueous Dispersions ◽

Innovative Methods ◽

Pharmaceutical Properties

The taste of drugs is an important factor affecting pharmacotherapy effectiveness, and obtaining formulations with acceptable organoleptic properties is still an ongoing issue in pharmaceutical technology. One of the innovative methods of taste masking is preparation of microparticles by the spray drying technique, utilizing polymers with different physicochemical properties. Rupatadine fumarate (RUP) is one of the newest antihistamines, with an innovative and multidirectional mechanism of action, and an extremely bitter taste. The aim of this work was to investigate the feasibility of utilizing organic or aqueous forms of ethylcellulose (EC) for the preparation of microparticles with RUP by the spray drying technique. Spray dried samples at different drug:polymer ratios were prepared using organic solution (Ethocel®) or aqueous dispersions of EC (Surelease®, Aquacoat® ECD). Evaluation of the taste masking efficacy was performed in vivo in human taste panel, in vitro based on dissolution test, and by self-constructed electronic tongue. It was shown that microparticles obtained from aqueous dispersions of EC have superior pharmaceutical properties in terms of both morphology and taste masking efficacy in comparison to those obtained from organic solution.

Download Full-text

Targeting AXL Kinase Sensitizes Leukemic Stem and Progenitor Cells to Venetoclax Treatment in Acute Myeloid Leukemia

Blood ◽

10.1182/blood.2020007651 ◽

2021 ◽

Author(s):

Xiaojia Niu ◽

Katharina Rothe ◽

Min Chen ◽

Sarah Grasedieck ◽

Rick Li ◽

...

Keyword(s):

Progenitor Cells ◽

Myeloid Leukemia ◽

Synergistic Effects ◽

Leukemic Cell ◽

Signaling Proteins ◽

Genetic Abnormalities ◽

Stem And Progenitor Cells ◽

Pharmaceutical Properties ◽

Pdx Models

The abundance of genetic abnormalities and phenotypic heterogeneities in AML pose significant challenges to developing improved treatments. Here we demonstrated that a key GAS6/AXL axis is highly activated in AML patient cells, particularly in stem/progenitor cells. We developed a potent, selective AXL inhibitor that has favorable pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation (PDX) models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in PDX models. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition or in combination with venetoclax potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells, which shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. Inhibition of AXL or BCL-2 also differentially targets key signaling proteins to synergize in leukemic cell killing. These findings have direct translational impact on the treatment of AML and other cancers with high AXL activity.

Download Full-text

Preclinical approaches in vulvovaginal candidiasis treatment with mucoadhesive thermoresponsive systems containing propolis

PLoS ONE ◽

10.1371/journal.pone.0243197 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243197

Author(s):

Amanda Pohlmann Bonfim ◽

Karina Mayumi Sakita ◽

Daniella Renata Faria ◽

Glaucia Sayuri Arita ◽

Franciele Abigail Vilugron Rodrigues Vendramini ◽

...

Keyword(s):

Vulvovaginal Candidiasis ◽

Fungal Resistance ◽

Vaginal Mucosa ◽

Childbearing Age ◽

Propolis Extract ◽

Low Toxicity ◽

Fluconazole Resistant ◽

Pharmaceutical Properties

Vulvovaginal candidiasis (VVC) is a common vaginitis that affects women, especially in childbearing age, caused by Candida albicans in almost 80% of cases. Considering the limited drug arsenal available and the increasing fungal resistance profile, the search for new therapeutic sources with low toxicity and easy administration should be supported. Propolis has been used as a traditional medicine for multiple diseases, considering its particular composition and pharmaceutical properties that permits its wide applicability; it has also emerged as a potential antifungal agent. Thus, this study performed an in vitro and in vivo investigation into the efficacy of a new mucoadhesive thermoresponsive platform for propolis delivery (MTS-PRPe) in a preclinical murine model of VVC treatment caused by C. albicans. The methodologies involved chemical analysis, an assessment of the rheological and mucoadhesive properties of propolis formulations, in vitro and in vivo antifungal evaluations, histological evaluations and electron microscopy of the vaginal mucosa. The results demonstrated the antifungal activity of propolis extract and MTS-PRP against the standard strain and a fluconazole-resistant clinical isolate of C. albicans, in both in vitro and in vivo assays. These results were similar and even better, depending on the propolis concentration, when compared to nystatin. Thus, the formulation containing propolis exhibited good performance against C. albicans in a vulvovaginal candidiasis experimental model, representing a promising opportunity for the treatment of this infection.

Download Full-text

Phytochemical Screening for Secondary Metabolites in Boswellia serrata Roxb. and Wrightia tinctoria (Roxb.) R.Br.

Notulae Scientia Biologicae ◽

10.15835/nsb649403 ◽

2014 ◽

Vol 6 (4) ◽

pp. 474-477 ◽

Cited By ~ 1

Author(s):

Prattipati SUBHASHINI DEVI ◽

Botcha SATYANARAYANA ◽

Maradana TARAKESWARA NAIDU

Keyword(s):

Secondary Metabolites ◽

Plant Species ◽

Large Scale ◽

In Vitro Production ◽

Boswellia Serrata ◽

Culture Techniques ◽

The Rich ◽

Pharmaceutical Properties ◽

Wrightia Tinctoria

Boswellia serrata, an important source of oleo-gum resin commonly known as Indian olibanum and Wrightia tinctoria are well documented for their pharmaceutical properties. Indiscriminate removal, difficulty in vegetative propagation and poor germination accounts for the depletion of useful plant species. Plant tissue culture techniques are used as an alternative method for the production of specific metabolites and also for the propagation of plant species at a large scale. In the present study preliminary screening for the presence of secondary metabolites was reported in order to understand the levels of phytochemicals, so that in vitro production of secondary metabolites using cell cultures will be initiated in future studies. Both qualitative and quantitative analysis of the two plants show the presence of all the three major groups of secondary metabolites, like nitrogen containing alkaloids, phenolic compounds like flavonoids, tannins, terpenes like steroids, saponins etc. Significant levels of all three major secondary metabolites were present in both species. However, higher activities of phenols (277.0±4.36), tannins (240.67±5.21), alkaloids (963.3±11.7) and flavonoids (150.0±2.89) were observed in B. serrata. All the three major groups of secondary metabolites in both species demonstrate the rich content of many useful biochemicals like pharmaceuticals, flavors, fragrances, agricultural chemicals etc. However, higher quantities in B. serrata indicates its richness in medicinal properties over W. tinctoria.

Download Full-text

Water-Soluble Ruthenium(III)-Dimethyl Sulfoxide Complexes: Chemical Behaviour and Pharmaceutical Properties

Metal-Based Drugs ◽

10.1155/mbd.1994.41 ◽

1994 ◽

Vol 1 (1) ◽

pp. 41-63 ◽

Cited By ~ 98

Author(s):

G. Mestroni ◽

E. Alessio ◽

G. Sava ◽

S. Pacor ◽

M. Coluccia ◽

...

Keyword(s):

Metastatic Tumor ◽

Water Soluble ◽

Spectroscopic Techniques ◽

Chemical Behavior ◽

Specific Cytotoxicity ◽

Chemical Behaviour ◽

Antitumor Properties ◽

Pharmaceutical Properties ◽

Almost All

In this paper we report a review of the results obtained in the last few years by our group in the development of ruthenium(III) complexes characterized by the presence of sulfoxide ligands and endowed with antitumor properties. In particular, we will focus on ruthenates of general formula Na[trans-RuCl4(R1R2SO)(L)], where R1R2SO = dimethylsulfoxide (DMSO) or tetramethylenesulfoxide (TMSO) and L = nitrogen donor ligand. The chemical behavior of these complexes has been studied by means of spectroscopic techniques both in slightly acidic distilled water and in phosphate buffered solution at physiological pH. The influence of biological reductants on the chemical behavior is also described. The antitumor properties have been investigated on a number of experimental tumors. Out of the effects observed, notheworthy appears the capability of the tested ruthenates to control the metastatic dissemination of solid metastasizing tumors. The analysis of the antimetastatic action, made in particular on the MCa mammary carcinoma of CBA mouse, has demonstrated a therapeutic value for these complexes which are able to significantly prolong the survival time of the treated animals. The antimetastatic effect is not attributable to a specific cytotoxicity for metastatic tumor cells although in vitro experiments on pBR322 double stranded DNA has shown that the test ruthenates bind to the macromolecule, causing breaks corresponding to almost all bases, except than thymine, and are able to cause interstrand bonds, depending on the nature of the complex being tested, some of which results active as cisplatin itself.

Download Full-text

Amidochelocardin Overcomes Resistance Mechanisms Exerted on Tetracyclines and Natural Chelocardin

Antibiotics ◽

10.3390/antibiotics9090619 ◽

2020 ◽

Vol 9 (9) ◽

pp. 619

Author(s):

Fabienne Hennessen ◽

Marcus Miethke ◽

Nestor Zaburannyi ◽

Maria Loose ◽

Tadeja Lukežič ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Efflux Pump ◽

Resistance Mechanism ◽

Tetracycline Resistance ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistance Breaking ◽

Pharmaceutical Properties ◽

Tract Infections

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.

Download Full-text

Facile Synthesis and In Vitro Activity of N-Substituted 1,2-Benzisothiazol-3(2H)-ones against Dengue Virus NS2BNS3 Protease

Pathogens ◽

10.3390/pathogens10040464 ◽

2021 ◽

Vol 10 (4) ◽

pp. 464

Author(s):

Farwa Batool ◽

Muhammad Saeed ◽

Hafiza Nosheen Saleem ◽

Luisa Kirschner ◽

Jochen Bodem

Keyword(s):

Dengue Virus ◽

Catalytic Triad ◽

Virus Infectivity ◽

Protease Inhibition ◽

One Pot ◽

Computational Docking ◽

Virus Serotype ◽

Ic50 Values ◽

Pharmaceutical Properties

Several new N-substituted 1,2-benzisothiazol-3(2H)-ones (BITs) were synthesised through a facile synthetic route for testing their anti-dengue protease inhibition. Contrary to the conventional multistep synthesis, we achieved structurally diverse BITs with excellent yields using a two-step, one-pot reaction strategy. All the synthesised compounds were prescreened for drug-like properties using the online Swiss Absorption, Distribution, Metabolism and Elimination (SwissADME) model, indicating their favourable pharmaceutical properties. Thus, the synthesised BITs were tested for inhibitory activity against the recombinant dengue virus serotype-2 (DENV-2) NS2BNS3 protease. Dose–response experiments and computational docking analyses revealed that several BITs bind to the protease in the vicinity of the catalytic triad with IC50 values in the micromolar range. The DENV2 infection assay showed that two BITs, 2-(2-chlorophenyl)benzo[d]isothiazol-3(2H)-one and 2-(2,6-dichlorophenyl)benzo[d]isothiazol-3(2H)-one, could suppress DENV replication and virus infectivity. These results indicate the potential of BITs for developing new anti-dengue therapeutics.

Download Full-text