The role of «proteolysis-antiproteolysis» system genes in occupational COPD development.

COPD is multifactorial disease, in which hereditary predisposition and environmental factors (including work conditions) play an important role. Among the genes associated with possible predisposition to COPD development a group of genes with the expression impacting the activity of “proteolysis-antiproteolysis – MMP2, MM9, TIMP2, A2M, ELN is considered. The main group of 72 underground coal miners with COPD (mean age 53,7±5,8 years, mean work experience – 21,8±4,8 years), and control group of 79 healthy miners (mean age – 48,2±5,6 years, mean work experience – 20,2±4,5 years) were examined. Polymorphism of genes with out bronchopulmonary pathology MMP9, α2M was revealed using PCR with electroforetic detection in agarosegel. Polymorphism of genes TIMP2, MMP2, ELN was revealed using PCR with fluorescent detection (RealTime PCR). By the data of molecular-genetic research among miners with COPD of occupational etiology (main group) and miners without it (control group) there was estabkished a reliable difference for the genotypes:MMP9*СС,TIMP2*GG; MMP9*СС,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Gly; MMP9*СС,MMP2*CТ,TIMP2*G/G,α2M*IIe/Val,ELN*Gly/Gly; MMP9*СС,MMP2*CС,TIMP2*G/G,α2M*IIe/Val,ELN*Ser/Se; MMP9*СТ,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Ser. These genotypes are associated with resistance for COPD development in underground coal miners ofUkraine. The obtained results testify to the participation of genes encoding protein synthesis of the system "proteolysantiproteolysis": MMP2, MMP9, TIMP2, A2M, ELN in the formation of genetic predisposition and resistance to the development of COPD of professional etiology in miners, which reveals new opportunities in the prevention of this disease in workers subject to the high concentrations of coal-rock dust

The role of «proteolysis-antiproteolysis» system genes in occupational COPD development.

COPD is multifactorial disease, in which hereditary predisposition and environmental factors (including work conditions) play an important role. Among the genes associated with possible predisposition to COPD development a group of genes with the expression impacting the activity of “proteolysis-antiproteolysis – MMP2, MM9, TIMP2, A2M, ELN is considered. The main group of 72 underground coal miners with COPD (mean age 53,7±5,8 years, mean work experience – 21,8±4,8 years), and control group of 79 healthy miners (mean age – 48,2±5,6 years, mean work experience – 20,2±4,5 years) were examined. Polymorphism of genes with out bronchopulmonary pathology MMP9, α2M was revealed using PCR with electroforetic detection in agarosegel. Polymorphism of genes TIMP2, MMP2, ELN was revealed using PCR with fluorescent detection (RealTime PCR). By the data of molecular-genetic research among miners with COPD of occupational etiology (main group) and miners without it (control group) there was estabkished a reliable difference for the genotypes: MMP9*СС,TIMP2*GG; MMP9*СС,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Gly; MMP9*СС,MMP2*CТ,TIMP2*G/G,α2M*IIe/Val,ELN*Gly/Gly; MMP9*СС,MMP2*CС,TIMP2*G/G,α2M*IIe/Val,ELN*Ser/Se; MMP9*СТ,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Ser. These genotypes are associated with resistance for COPD development in underground coal miners ofUkraine. The obtained results testify to the participation of genes encoding protein synthesis of the system "proteolysantiproteolysis": MMP2, MMP9, TIMP2, A2M, ELN in the formation of genetic predisposition and resistance to the development of COPD of professional etiology in miners, which reveals new opportunities in the prevention of this disease in workers subject to the high concentrations of coal-rock dust

Primary Screening of the Biological Activity of Heterocyclic Aminoderivatives of 2,3-dichloro-1,4-naphtoquinone

The aim. Check the antimicrobial and fungicidal activity of 2,3-dichloro-1,4-naphthoquinone aminopyrazole derivatives and predict their severity of toxicity to rats.Materials and methods of the research. The antimicrobial activity of heterocyclic amino derivatives of naphthoquinone 3a-d was studied by diffusion of the substance into agar on solid nutrient medium and by serial dilution. Acute rodent toxicity was determined by the QSAR simulation method implemented in GUSAR software.Results. In the work, the antimicrobial and fungicidal activities of new heterocyclic amino derivatives of naphthoquinone were studied, as well as the in silico determination of their acute toxicity for rats was carried out using four types of substance administration.Conclusions. The study of aminopyrazole derivatives of naphthoquinone revealed the compounds exhibiting high antimicrobial activity against the Candida tenuis test culture, namely: 2-chloro-3-((1-methyl-1H-pyrazol-4-yl) amino) naphthalene-1,4-dione (3a) and 2-chloro-3 - ((1-methyl-1H-pyrazol-3-yl) amino) naphthalene-1,4-dione (3b). All the synthesized compounds were found to exhibit selective bacterio- and fungistatic activity. QSAR determined the non-toxic compound 3c in the intraperitoneal route of administration, as well as the non-toxic compound 3d in the subcutaneous route of administrationМета. Провести дослідження антимікробної та фунгіцидної активностей амінопіразольних похідних 2,3-дихлоро-1,4-нафтохінону та спрогнозувати їхню гостру токсичність.Матеріали та методи дослідження. Протимікробну активність гетероциклічних амінопохідних нафтохінону 3a-d вивчали шляхом дифузії речовини в агар на твердому поживному середовищі та методом серійних розведень. Гостру токсичність для гризунів визначали методом моделювання QSAR, реалізованим в програмному забезпеченні GUSAR .Результати. У роботі досліджено антимікробну та фунгіцидну активності нових гетероциклічних амінопохідних нафтохінону, а також проведено визначення їх in silico гострої токсичності для щурів за чотирма типами введення субстанції.Висновки. Дослідження амінопіразольних похідних нафтохінону дозволило виявити сполуки, які проявляють високу антимікробну активність по відношенню до тест-культури Candida tenuis, а саме: 2-хлоро-3-((1-метил-1Н-піразол-4-іл)аміно)нафтален-1,4-діон 3a та 2-хлоро-3-((1-метил-1Н-піразол-3-іл)аміно)нафтален-1,4-діон 3b. Встановлено, що усі синтезовані сполуки проявляють вибіркову бактеріо- і фунгістатичну активності. Визначено методом QSAR нетоксичну сполуку 3с при внутрішньочеревному шляху введення, а також нетоксичну сполуку 3d при підшкірному шляху введенн