Scientific Center for Anti Infectious Drugs

Almaty, Kazakhstan

Scientific Center for Anti Infectious Drugs

Almaty, Kazakhstan
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Ilin A.I.,Scientific Center for Anti Infectious Drugs | Kulmanov M.E.,Scientific Center for Anti Infectious Drugs | Korotetskiy I.S.,Scientific Center for Anti Infectious Drugs | Islamov R.A.,Scientific Center for Anti Infectious Drugs | And 3 more authors.
Frontiers in Cellular and Infection Microbiology | Year: 2017

Drug induced reversion of antibiotic resistance is a promising way to combat multidrug resistant infections. However, lacking knowledge of mechanisms of drug resistance reversion impedes employing this approach in medicinal therapies. Induction of antibiotic resistance reversion by a new anti-tuberculosis drug FS-1 has been reported. FS-1 was used in this work in combination with standard anti-tuberculosis antibiotics in an experiment on laboratory guinea pigs infected with an extensively drug resistant (XDR) strain Mycobacterium tuberculosis SCAID 187.0. During the experimental trial, genetic changes in the population were analyzed by sequencing of M. tuberculosis isolates followed by variant calling. In total 11 isolates obtained from different groups of infected animals at different stages of disease development and treatment were sequenced. It was found that despite the selective pressure of antibiotics, FS-1 caused a counter-selection of drug resistant variants that speeded up the recovery of the infected animals from XDR tuberculosis. Drug resistance mutations reported in the genome of the initial strain remained intact in more sensitive isolates obtained in this experiment. Variant calling in the sequenced genomes revealed that the drug resistance reversion could be associated with a general increase in genetic heterogeneity of the population of M. tuberculosis. Accumulation of mutations in PpsA and PpsE subunits of phenolpthiocerol polyketide synthase was observed in the isolates treated with FS-1 that may indicate an increase of persisting variants in the population. It was hypothesized that FS-1 caused an active counter-selection of drug resistant variants from the population by aggravating the cumulated fitness cost of the drug resistance mutations. Action of FS-1 on drug resistant bacteria exemplified the theoretically predicted induced synergy mechanism of drug resistance reversion. An experimental model to study the drug resistance reversion phenomenon is hereby introduced. © 2017 Ilin, Kulmanov, Korotetskiy, Islamov, Akhmetova, Lankina and Reva.


Nersesyan A.,Medical University of Vienna | Ilin A.,Scientific Center for Anti Infectious Drugs | Kulmanov M.,Scientific Center for Anti Infectious Drugs
Cytology and Genetics | Year: 2011

A very promising antiviral and antimicrobial agent FS-1 was studied for its ability to induce DNA damage and micronuclei in human tumor cell lines HeLa and Caco-2 at concentrations of 200, 500 and 1000 μg/ml without exogenous metabolic activation. The compound was additionally tested for DNA damaging ability in human lymphocytes at concentrations of 200, 400 and 800 μg/ml. Neither DNA damage nor micronucleus formation was observed after treatment of all types of cells with FS-1. Based on these results, FS-1 can be further studied for its safety to humans for potential application in clinical medicine as an antimicrobial/antiviral drug. © Allerton Press, Inc., 2011.


PubMed | Scientific Center for Anti Infectious Drugs and University of Pretoria
Type: Journal Article | Journal: Genome announcements | Year: 2015

Complete genome sequence of the multidrug-resistant clinical isolate Mycobacterium tuberculosis SCAID 187.0 containing several drug-resistance mutations is presented. This strain is used in experiments to study genomic and population changes leading to reversion of susceptibility to the 1st line anti-tuberculosis (TB) drugs under the influence of a new medicinal drug FS-1.


Ilin A.,Scientific Center for Anti Infectious Drugs | Kulmanov M.,Scientific Center for Anti Infectious Drugs | Nersesyan A.,Medical University of Vienna | Stopper H.,Institute of Toxicology and Pharmacology
Journal of B.U.ON. | Year: 2015

Purpose: The purpose of this study was to determine possible genotoxic effects of a new very promising antibacterial/antiviral drug FS-1. Methods: The drug was tested in TA98, TA100, TA102, TA1535 and TA1537 strains of Salmonella (Ames test) with and without metabolic activation, and also in mouse lymphoma L5178Y cells by means of micronucleus and comet assays. In microbes the drug was tested at concentrations up to 500 ug/plate and in mouse lymphoma cells up to 2, 000 ug/ml. Results: In both test-systems in all experiments completely negative results were obtained although FS-1 was tested at maximum tolerated doses. Conclusions: The drug is not genotoxic. This is advantageous because many antibacterial/antiviral drugs possess such activity.


Ilin A.I.,Scientific Center for Anti Infectious Drugs | Parsadanyan G.G.,Yerevan State Medical University | Nersesyan A.K.,Medical University of Vienna
New Armenian Medical Journal | Year: 2013

The analysis of literature shows that all halogens can react with important biological macromolecules, such as DNA and RNA. The consequences of mentioned reactions can be different, i.e., both protection from further toxic stimuli and toxic (mutagenic and possibly carcinogenic) effects. All halogens are geno-toxic, but induce this effect only at high doses not relevant for humans. The biological consequences of such reactions of halogens with deoxyribonucleic and ribonucleic acids and chromosomes warrant further investigations.


Kabanikhin S.I.,Novosibirsk State University | Voronov D.A.,Novosibirsk State University | Krivorotko O.I.,Novosibirsk State University | Belonog A.Yu.,Novosibirsk State University | Ilyin A.I.,Scientific Center for Anti infectious Drugs
Proceedings - 2015 International Conference on Biomedical Engineering and Computational Technologies, SIBIRCON 2015 | Year: 2015

The minimal model of insulin secretion based on C-peptide data (Toffolo et al., 1995) is presented in this report. The secretion model is identified on C-peptide taken in plasma; it must be integrated into a model of whole-body C-peptide kinetics. The kinetic model is the one proposed by (Eaton et al., 1980) and consists of 2 compartments. Compartment 1, accessible to measurement, represents plasma and rapidly equilibrating tissues, whereas compartment 2 represents tissues in slow exchange with plasma. This model allows estimating distribution of insulin in the blood and tissues. A new iterative algorithm for finding kinetic constants and secretion parameters is proposed. Numerical solution of inverse problem was obtained by using synthetic data. Different levels of noise were added to such data. The question of initial approximation is covered in this talk). © 2015 IEEE.


Kalykova A.S.,Kazakh National Medical University | Kalykova A.S.,Scientific Center for Anti infectious Drugs | Vetchy D.,University of Veterinary And Pharmaceutical Sciences Brno | Sakipova Z.B.,Kazakh National Medical University
Research Journal of Pharmaceutical, Biological and Chemical Sciences | Year: 2015

The original substance of the FS-1 is a nano-ion complex with bactericidal and virucidal activity which was developed in Scientific Center for Anti-infectious Drugs (Almaty, RK) and is intended for the treatment of tuberculosis. The purpose of presented work was to develop a rational and optimum technology for preparing of tablets based on the substance of FS-1, and to evaluate the effect of the time of hydrolysis on quality of the developed medical form. For this, 2 batches of FS-1 substance with time of hydrolysis 17 min and 20 min were synthesized. The aim was to obtain tablets with suitable mechanical properties (friability below 1%) and a suitable disintegration time (up to 15 min), as is required by the Ph. Eur. Optimal formulation and process parameters for the preparation of tablets containing FS-1, under which tablets met the requirements for tablet disintegration time, tablet friability, and tablet mass and content uniformity, were identified within presented work. Longer time of hydrolysis of FS-1 substance probably led to unsuitable conversion of iodine into iodide form.


Ilin A.,Scientific Center for Anti Infectious Drugs | Nersesyan A.,Medical University of Vienna
Archive of Oncology | Year: 2013

Iodine is necessary for all living organisms. Deficiency of iodine in the organism leads to various diseases (including mental) and increased rates of cancer. It is well known that one third of the world's population lived in iodine-deficient areas. At present time, the primary intervention for preventing iodine deficiency disorders worldwide is through the iodization of salt. The two most common types of fortificant used to iodize salt are potassium iodide and potassium iodate. Iodine-containing compounds are also widely used in clinical medicine as a highly effective topical antimicrobial agent that has been used clinically in the treatment of wounds. Hence, the genetic toxicology of iodine and iodine-containing compounds is very essential topic. In this literature review are analyzed the data concerning genetic toxicology and the influence of these compounds on tumor rates in epidemiological and experimental studies. © 2013, Oncology Institute of Vojvodina, Sremska Kamenica.


Bogdanov A.Yu.,Scientific Center for Anti Infectious Drugs | Bogdanova T.M.,Scientific Center for Anti Infectious Drugs | Ilin A.I.,Scientific Center for Anti Infectious Drugs
Cytology and Genetics | Year: 2014

The endocytic pathway of alpha-fetoprotein (AFP) in three types of mouse bone marrow hematopoietic stem cells (HSCs) different by the degree of maturity is similar to the natural pathway: it is based on receptor-mediated tranasport through the membrane p60, p65, and p305 AFP receptors with a clathrin-dependent mechanism of receptosome organization, in the formation and generation of which the AP-2 complex, endofilin, and dynamin are involved. In the studied types of HSCs, nongradient AFP was recorded in the Golgi complex, where it appeared by merging with the formed receptosome, as well as in the cytoplasm, endoplasmatic reticulum, and mitochondria, presumably through consequent binding with cytoplasmic carrier proteins (p55, p52, p62, and p67 AFP receptors) and also to transorganelle transporter proteins (p145 and p182 AFP receptors). A study of the role of AFP endocytosis in the modification of the biological activity of the studied HSC types has shown that it directly regulates protein synthesis and metabolic activity, while its effect on other examined types of biological activity was mediated by ERK1/2. © 2014 Allerton Press, Inc.


PubMed | Scientific Center for Anti Infectious Drugs
Type: Journal Article | Journal: Journal of B.U.ON. : official journal of the Balkan Union of Oncology | Year: 2015

The purpose of this study was to determine possible genotoxic effects of a new very promising antibacterial/antiviral drug FS-1.The drug was tested in TA98, TA100, TA102, TA1535 and TA1537 strains of Salmonella (Ames test) with and without metabolic activation, and also in mouse lymphoma L5178Y cells by means of micronucleus and comet assays. In microbes the drug was tested at concentrations up to 500 g/plate and in mouse lymphoma cells up to 2,000 g/ml.In both test-systems in all experiments completely negative results were obtained although FS-1 was tested at maximum tolerated doses.The drug is not genotoxic. This is advantageous because many antibacterial/antiviral drugs possess such activity.

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