10 research outputs found
Π‘ΠΈΠ½ΡΠ΅Π·, ΠΏΡΠΎΡΠΈΠΌΡΠΊΡΠΎΠ±Π½Π° Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΡΠ° Π΄ΠΎΠΊΡΠ½Π³ΠΎΠ²Ρ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ 6-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2- ΡΠ»)-5-ΠΌΠ΅ΡΠΈΠ»ΡΡΡΠ½ΠΎ[2,3-d]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-4(3H)-ΠΎΠ½ΡΠ² Π· Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄Π½ΠΈΠΌΠΈ ΡΠ° 1,2,4-ΠΎΠΊΡΠ°Π΄ΡΠ°Π·ΠΎΠ»-5- ΡΠ»ΠΌΠ΅ΡΠΈΠ»ΡΠ½ΠΈΠΌΠΈ Π·Π°ΠΌΡΡΠ½ΠΈΠΊΠ°ΠΌΠΈ
Aim. To synthesize, study the antimicrobial activity and suggest antimicrobial activity mechanism for the novel derivatives of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one. Results and discussion. As the result of the targeted modification of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]-pyrimidin-4(3H)-one in position 3 with acetamide and 1,2,4-oxadiazol-5-ylmethyl substituents, the compounds, which demonstrated better antimicrobial activity in the agar well diffusion assay than the reference drug Streptomycin, were obtained. To elucidate the mechanism of action of the novel compounds, the docking studies were con-ducted to the active site of the 16S subunit of ribosomal RNA, the proven target for aminoglycoside antibiotics, as well as tRNA (Guanine37-N1)-methyltransferase (TrmD), which inhibitors were considered as a new potential class of antibiotics. Experimental part. By the interaction of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one with a series of N-arylchloroacetamides and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in DMF in the presence of K2CO3 the target compounds were obtained. The antimicrobial activity was assessed by the agar well diffusion method. The concentration of microbial cells was determined by the McFarland standard; the value was 107 cells in 1 mL of the media. The 18βββ24 hour culture of microorganisms was used for tests. For the bacteria cultivation, MΓΌller-Hinton agar was used, Sabouraud agar was applied for C. albicans cultivation. The compounds were tested as the DMSO solution with the concentration of 100 Β΅g/mL; the volume of the solution was 0.3 mL, the same volume was used for Streptomycin (the concentration 30 Β΅g/mL). The docking studies were performed using Autodock Vina. Crystallographic data for the complexes of Streptomycin with the 16S subunit of ribosomal RNA (1NTB) and its active site, as well as for tRNA (Guanine37-N1)-methyltransferase (EC 2.1.1.228; TrmD) (5ZHN) and its active site were obtained from the Protein Data Bank.Conclusions. It has been determined that 2-[6-(1H-benzimidazol-2-yl)-5-methyl-4-oxothieno[2,3-d]pyrimidin-3(4H)-yl]-N-[4-(ethoxy)phenyl]acetamide, which is the most active as an antimicrobial agent among the compounds tested, also shows the best binding activity towards the active site of tRNA (guanine37-N1)-methyltransferase.ΠΠ΅ΡΠ°. Π‘ΠΈΠ½ΡΠ΅Π·ΡΠ²Π°ΡΠΈ ΠΉ Π΄ΠΎΡΠ»ΡΠ΄ΠΈΡΠΈ ΠΏΡΠΎΡΠΈΠΌΡΠΊΡΠΎΠ±Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ Π½ΠΎΠ²ΠΈΡ
ΠΏΠΎΡ
ΡΠ΄Π½ΠΈΡ
6-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)-5-ΠΌΠ΅ΡΠΈΠ»ΡΡΡΠ½ΠΎ[2,3-d]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-4(3H)-ΠΎΠ½ΡΠ² ΡΠ° Π·Π°ΠΏΡΠΎΠΏΠΎΠ½ΡΠ²Π°ΡΠΈ ΠΌΠ΅Ρ
Π°Π½ΡΠ·ΠΌ ΠΏΡΠΎΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ ΡΠ° ΡΡ
ΠΎΠ±Π³ΠΎΠ²ΠΎΡΠ΅Π½Π½Ρ. Π£ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΡΠ»Π΅ΡΠΏΡΡΠΌΠΎΠ²Π°Π½ΠΎΡ ΠΌΠΎΠ΄ΠΈΡΡΠΊΠ°ΡΡΡ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½Π½Ρ 3 6-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)-5-ΠΌΠ΅ΡΠΈΠ»ΡΡΡΠ½ΠΎ[2,3-d]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-4(3H)-ΠΎΠ½Ρ Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄Π½ΠΈΠΌ ΡΠ° 1,2,4-ΠΎΠΊΡΠ°Π΄ΡΠ°Π·ΠΎΠ»-5-ΡΠ»ΠΌΠ΅ΡΠΈΠ»ΡΠ½ΠΈΠΌ Π·Π°ΠΌΡΡΠ½ΠΈΠΊΠ°ΠΌΠΈ Π±ΡΠ»ΠΎ ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΎ ΡΠΏΠΎΠ»ΡΠΊΠΈ Π· Π²ΠΈΠ·Π½Π°ΡΠ΅Π½ΠΎΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π΄ΠΈΡΡΠ·ΡΡ Π² Π°Π³Π°Ρ ΠΏΡΠΎΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ, ΡΠΎ Ρ Π±ΡΠ»ΡΡΠΎΡ Π·Π° Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΠΏΠΎΡΡΠ²Π½ΡΠ½Π½Ρ Π‘ΡΡΠ΅ΠΏΡΠΎΠΌΡΡΠΈΠ½Ρ. Π ΠΌΠ΅ΡΠΎΡ Π·βΡΡΡΠ²Π°Π½Π½Ρ ΠΌΠ΅Ρ
Π°Π½ΡΠ·ΠΌΡ Π΄ΡΡ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ Π±ΡΠ»ΠΎ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π΄ΠΎΠΊΡΠ½Π³ΠΎΠ²Ρ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ ΡΠΎΠ΄ΠΎ Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΠ°ΠΉΡΡ ΡΡΠ±ΠΎΠ΄ΠΈΠ½ΠΈΡΡ 16S ΡΠΈΠ±ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΠΎΡ Π ΠΠ, ΡΠΊΠ° Ρ ΠΏΡΠ΄ΡΠ²Π΅ΡΠ΄ΠΆΠ΅Π½ΠΎΡ ΠΌΡΡΠ΅Π½Π½Ρ Π΄Π»Ρ Π°ΠΌΡΠ½ΠΎΠ³Π»ΡΠΊΠΎΠ·ΠΈΠ΄Π½ΠΈΡ
Π°Π½ΡΠΈΠ±ΡΠΎΡΠΈΠΊΡΠ², Π° ΡΠ°ΠΊΠΎΠΆ ΡΠ ΠΠ (ΠΡΠ°Π½ΡΠ½-37-N1)-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π·ΠΈ (TrmD), ΡΠ½Π³ΡΠ±ΡΡΠΎΡΠΈ ΡΠΊΠΎΡ ΡΠΎΠ·Π³Π»ΡΠ΄Π°ΡΡΡΡΡ ΡΠΊ Π½ΠΎΠ²ΠΈΠΉ ΠΏΠΎΡΠ΅Π½ΡΡΠΉΠ½ΠΈΠΉ ΠΊΠ»Π°Ρ Π°Π½ΡΠΈΠ±ΡΠΎΡΠΈΠΊΡΠ².
ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π° ΡΠ°ΡΡΠΈΠ½Π°. Π¨Π»ΡΡ
ΠΎΠΌ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ 6-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)-5-ΠΌΠ΅ΡΠΈΠ»ΡΡΡΠ½ΠΎ[2,3-d]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-4(3H)-ΠΎΠ½Ρ Π· ΡΡΠ΄ΠΎΠΌ N-Π°ΡΠΈΠ»Ρ
Π»ΠΎΡΠΎΠ°ΡΠ΅ΡΠ°ΠΌΡΠ΄ΡΠ² ΡΠ° 3-Π°ΡΠΈΠ»-5-(Ρ
Π»ΠΎΡΠΎΠΌΠ΅ΡΠΈΠ»)-1,2,4-ΠΎΠΊΡΠ°Π΄ΡΠ°Π·ΠΎΠ»ΡΠ² Π² ΡΠΌΠΎΠ²Π°Ρ
ΠΠΠ€Π-K2CO3 Π±ΡΠ»ΠΎ ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΎ ΡΡΠ»ΡΠΎΠ²Ρ ΡΠΏΠΎΠ»ΡΠΊΠΈ. ΠΠ½ΡΠΈΠΌΡΠΊΡΠΎΠ±Π½Ρ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ Π²ΠΈΠ·Π½Π°ΡΠ°Π»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π΄ΠΈΡΡΠ·ΡΡ Π² Π°Π³Π°Ρ. ΠΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΡΡ ΠΌΡΠΊΡΠΎΠ±Π½ΠΈΡ
ΠΊΠ»ΡΡΠΈΠ½ Π²ΠΈΠ·Π½Π°ΡΠ°Π»ΠΈ Π·Π° ΠΠ°ΠΊΠ€Π°ΡΠ»Π°Π½Π΄ΠΎΠΌ; ΠΌΡΠΊΡΠΎΠ±Π½Π΅ Π½Π°Π²Π°Π½ΡΠ°ΠΆΠ΅Π½Π½Ρ ΡΠΊΠ»Π°Π»ΠΎ 107 ΠΌΡΠΊΡΠΎΠ±Π½ΠΈΡ
ΠΎΠ΄ΠΈΠ½ΠΈΡΡ Π² 1 ΠΌΠ» ΡΠ΅ΡΠ΅Π΄ΠΎΠ²ΠΈΡΠ°. ΠΠ»Ρ ΡΠ΅ΡΡΡΠ² Π²ΠΈΠΊΠΎΡΠΈΡΡΠΎΠ²ΡΠ²Π°Π»ΠΈ 18βββ24 Π³ΠΎΠ΄ΠΈΠ½Π½Ρ ΠΊΡΠ»ΡΡΡΡΡ ΠΌΡΠΊΡΠΎΠΎΡΠ³Π°Π½ΡΠ·ΠΌΡΠ². ΠΠ»Ρ ΠΊΡΠ»ΡΡΠΈΠ²ΡΠ²Π°Π½Π½Ρ Π±Π°ΠΊΡΠ΅ΡΡΠΉ Π²ΠΈΠΊΠΎΡΠΈΡΡΠΎΠ²ΡΠ²Π°Π»ΠΈ Π°Π³Π°Ρ ΠΡΠ»Π»Π΅ΡΠ°-ΠΡΠ½ΡΠΎΠ½Π°; Π΄Π»Ρ ΠΊΡΠ»ΡΡΠΈΠ²ΡΠ²Π°Π½Π½Ρ C. albicans Π²ΠΈΠΊΠΎΡΠΈΡΡΠΎΠ²ΡΠ²Π°Π»ΠΈ Π°Π³Π°Ρ Π‘Π°Π±ΡΡΠΎ. Π‘ΠΏΠΎΠ»ΡΠΊΠΈ Π²Π²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π΄ΠΈΡΡΠ·ΡΡ Π² Π°Π³Π°Ρ (Π»ΡΠ½ΠΊΠ°ΠΌΠΈ) Ρ Π²ΠΈΠ³Π»ΡΠ΄Ρ ΡΠΎΠ·ΡΠΈΠ½Ρ Ρ ΠΠΠ‘Π Π² ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΡΡ 100 ΠΌΠΊΠ³/ΠΌΠ» Π² ΠΎΠ±βΡΠΌΡ 0,3 ΠΌΠ»; Π°Π½Π°Π»ΠΎΠ³ΡΡΠ½ΠΈΠΉ ΠΎΠ±βΡΠΌ Π²ΠΈΠΊΠΎΡΠΈΡΡΠΎΠ²ΡΠ²Π°Π»ΠΈ Π΄Π»Ρ Π‘ΡΡΠ΅ΠΏΡΠΎΠΌΡΡΠΈΠ½Ρ (ΠΊΠΎΠ½Ρ. 30 ΠΌΠΊΠ³/ΠΌΠ»). ΠΠΎΠΊΡΠ½Π³ΠΎΠ²Ρ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π·Π° Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΠΎΡ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΈ Autodock Vina. ΠΡΠΈΡΡΠ°Π»ΠΎΠ³ΡΠ°ΡΡΡΠ½Ρ Π΄Π°Π½Ρ Π΄Π»Ρ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΡΠ² ΡΡΡΠ΅ΠΏΡΠΎΠΌΡΡΠΈΠ½Ρ Π· 16S ΡΡΠ±ΠΎΠ΄ΠΈΠ½ΠΈΡΠ΅Ρ ΡΠΈΠ±ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΠΎΡ Π ΠΠ (1NTB) ΡΠ° ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΠ°ΠΉΡΡ Ρ Π΄Π»Ρ ΡΠ ΠΠ (ΠΡΠ°Π½ΡΠ½-37-N1)-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π·ΠΈ (EC 2.1.1.228; TrmD) (5ZHN) ΡΠ° ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ ΡΠ°ΠΉΡΡ Π±ΡΠ»ΠΎ ΠΎΡΡΠΈΠΌΠ°Π½ΠΎ Π· Protein Data Bank.ΠΠΈΡΠ½ΠΎΠ²ΠΊΠΈ. ΠΠΈΡΠ²Π»Π΅Π½ΠΎ, ΡΠΎ ΡΠΏΠΎΠ»ΡΠΊΠ° 2-[6-(1H-Π±Π΅Π½Π·ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-2-ΡΠ»)-5-ΠΌΠ΅ΡΠΈΠ»-4-ΠΎΠΊΡΠΎΡΡΡΠ½ΠΎ[2,3-d]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-3(4H)-ΡΠ»]-N-[4-(Π΅ΡΠΎΠΊΡΠΈ)ΡΠ΅Π½ΡΠ»]Π°ΡΠ΅ΡΠ°ΠΌΡΠ΄, ΡΠΊΠ° Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΡΡΡ Π½Π°ΠΉΠ±ΡΠ»ΡΡΠΎΡ ΠΏΡΠΎΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ, Ρ Π΄ΠΎΠΊΡΠ½Π³ΠΎΠ²ΠΈΡ
ΡΠΎΠ·ΡΠ°Ρ
ΡΠ½ΠΊΠ°Ρ
Ρ ΡΠ°ΠΊΠΎΠΆ Π½Π°ΠΉΠ±ΡΠ»ΡΡ Π΅ΡΠ΅ΠΊΡΠΈΠ²Π½ΠΈΠΌ ΡΠ½Π³ΡΠ±ΡΡΠΎΡΠΎΠΌ ΡΠ ΠΠ (ΠΡΠ°Π½ΡΠ½-37-N1)-ΠΌΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π·ΠΈ
Influence of reagents mixture density on the radiation-thermal synthesis of lithium-zinc ferrites
Influence of Li[2]CO[3]-ZnO-Fe[2]O[3] powder reagents mixture density on the synthesis efficiency of lithium-zinc ferrites in the conditions of thermal heating or pulsed electron beam heating was studied by X-Ray diffraction and magnetization analysis. The results showed that the including a compaction of powder reagents mixture in ferrite synthesis leads to an increase in concentration of the spinel phase and decrease in initial components content in lithium-substituted ferrites synthesized by thermal or radiation-thermal heating
Effect of powder compaction on radiation-thermal synthesis of lithium-titanium ferrites
Effect of powder compaction on the efficiency of thermal and radiation-thermal synthesis of lithium-substituted ferrites was investigated by X-Ray diffraction and specific magnetization analysis. It was shown that the radiation-thermal heating of compacted powder reagents mixture leads to an increase in efficiency of lithium-titanium ferrites synthesis
Synthesis and Antimicrobial Activity of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones
The aim of this work is to study methods of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones preparation and their antimicrobial activity.Materials and methods. 1Π NMR spectra were recorded on Varian Mercury-200 (200 MHz), 13C NMR spectra were acquired on Bruker Avance 500 1H NMR (500 MHz) and 13C NMR (125 MHz) in DMSO-d6 and CDCl3. LC-MS analysis of compounds was performed on an Agilent 1100 HPLC instrument with chemical ionization at atmospheric pressure (APCI). The study of antimicrobial activity of compounds was performed by agar well diffusion method. The docking studies were performed using Autodock Vina.Results and discussion. The interaction of 3-(2-bromopropanoyl)-2H-chromen-2-ones with N-substituted thioureas produced novel derivatives of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)chromen-2-ones. The study of antimicrobial activity of the obtained compounds allowed to identify active samples against E. Ρoli and P. aeruginosa strains. Among the tested compounds, 8-methoxy-3-{2-[(2-methoxyphenyl)amino]-5-methyl-1,3-thiazol-4-yl}-2H-chromen-2-one showed higher activity than the reference drug Streptomycin against E. coli strain. Some compounds showed high activity against P. aeruginosa. Docking studies of the synthesized compounds indicated that they can bind in the active site to bacterial tRNA (guanine37-N1)-methyltransferase.Conclusions. Novel derivatives of 2H-chromen-2-ones with 2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol moiety at the position 3 were obtained by the Hantzsch thiazole synthesis starting from 3-(2-bromopropanoyl)-2H-chromen-2-ones. Studies of antimicrobial activity allowed to identify new 2H-chromen-2-one derivatives as equipotent antimicrobial agents to the reference drug Streptomycin or even more potent. The docking studies revealed that the synthesized compounds may be inhibitors of tRNA (guanine37-N1)-methyltransferase, which is a crucial enzyme for survival of different bacteria, e.g. P. aeruginosa during stress condition
Synthesis and Antimicrobial Activity of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones
The aim of this work is to study methods of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones preparation and their antimicrobial activity.Materials and methods. 1Π NMR spectra were recorded on Varian Mercury-200 (200 MHz), 13C NMR spectra were acquired on Bruker Avance 500 1H NMR (500 MHz) and 13C NMR (125 MHz) in DMSO-d6 and CDCl3. LC-MS analysis of compounds was performed on an Agilent 1100 HPLC instrument with chemical ionization at atmospheric pressure (APCI). The study of antimicrobial activity of compounds was performed by agar well diffusion method. The docking studies were performed using Autodock Vina.Results and discussion. The interaction of 3-(2-bromopropanoyl)-2H-chromen-2-ones with N-substituted thioureas produced novel derivatives of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)chromen-2-ones. The study of antimicrobial activity of the obtained compounds allowed to identify active samples against E. Ρoli and P. aeruginosa strains. Among the tested compounds, 8-methoxy-3-{2-[(2-methoxyphenyl)amino]-5-methyl-1,3-thiazol-4-yl}-2H-chromen-2-one showed higher activity than the reference drug Streptomycin against E. coli strain. Some compounds showed high activity against P. aeruginosa. Docking studies of the synthesized compounds indicated that they can bind in the active site to bacterial tRNA (guanine37-N1)-methyltransferase.Conclusions. Novel derivatives of 2H-chromen-2-ones with 2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol moiety at the position 3 were obtained by the Hantzsch thiazole synthesis starting from 3-(2-bromopropanoyl)-2H-chromen-2-ones. Studies of antimicrobial activity allowed to identify new 2H-chromen-2-one derivatives as equipotent antimicrobial agents to the reference drug Streptomycin or even more potent. The docking studies revealed that the synthesized compounds may be inhibitors of tRNA (guanine37-N1)-methyltransferase, which is a crucial enzyme for survival of different bacteria, e.g. P. aeruginosa during stress condition
Synthesis, in silico and in vitro antimicrobial activity of N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides
According to the recent studies bezylcarboxamide fragment attached to the thiophene ring of thieno[2,3-d]pyrimidine is beneficial for antimicrobial activity of the compounds. Therefore we focused our efforts on constructing of the simple molecules such as N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides to get deeper insight into their antimicrobial activity. As the optimal procedure for preparation of target compounds we choose 1,1β-carbonyldiimidazole promoted interaction of 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid with the series of substituted benzyl amines. The obtained amides showed good activity against the strains of S. aureus and B. subtilis, which was higher for the derivative without substituents in benzene ring or the compounds with small substituents like methyl or methoxyl groups in the para-position of the benzene ring. Docking studies showed that despite the good values of the scoring functions, the conformational analysis of the ligandsβ poses in the active site revealed their ability for only partial inhibition of TrmD of P. aeruginosa
Synthesis, in silico and in vitro antimicrobial activity of N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides
According to the recent studies bezylcarboxamide fragment attached to the thiophene ring of thieno[2,3-d]pyrimidine is beneficial for antimicrobial activity of the compounds. Therefore we focused our efforts on constructing of the simple molecules such as N-(benzyl)-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamides to get deeper insight into their antimicrobial activity. As the optimal procedure for preparation of target compounds we choose 1,1β-carbonyldiimidazole promoted interaction of 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxylic acid with the series of substituted benzyl amines. The obtained amides showed good activity against the strains of S. aureus and B. subtilis, which was higher for the derivative without substituents in benzene ring or the compounds with small substituents like methyl or methoxyl groups in the para-position of the benzene ring. Docking studies showed that despite the good values of the scoring functions, the conformational analysis of the ligandsβ poses in the active site revealed their ability for only partial inhibition of TrmD of P. aeruginosa
Synthesis and Antimicrobial Evaluation of 2-(6-Imidazo[1,2-a]pyridin-2-yl-5-methyl-2,4-dioxo-3-phenyl-3,4-dihydrothieno[2,3-d]pyrimidin-1(2H)-yl)-N-arylacetamide Derivatives
6-Heteryl-5-methylthieno[2,3-d]pyrimidin-2,4(1H,3H)-diones are of great interest as the promising objects for the search of antibacterials. In this communication, we obtained 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione by interaction of 6-(bromoacetyl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione with 2-aminopyridine. The obtained heterocyclic hybrid was further modified by alkylation with 2-chloroarylacetamides. Antimicrobial activity studies for the synthesized compounds using the agar well diffusion method revealed their moderate activity against S. aureus, E. coli and B. subtilis. According to the double dilution assay MIC value results for 6-(imidazo[1,2-a]pyridin-2-yl)-5-methyl-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneagainst P. aeruginosa was less than the value determined for the reference drug streptomycin. The docking study of the synthesized compounds to the active site of TrmD isolated from P. aeruginosa did not show their effective inhibitory activity
Design, Synthesis and In Vitro Antimicrobial Activity of 6-(1<i>H</i>-Benzimidazol-2-yl)-3,5-dimethyl-4-oxo-2-thio-3,4-dihydrothieno[2,3-<i>d</i>]pyrimidines
The rapid development in bacterial resistance to many groups of known antibiotics forces the researchers to discover antibacterial drug candidates with previously unknown mechanisms of action, one of the most relevant being the inhibition of tRNA (Guanine37-N1)-methyltransferase (TrmD). The discovery of selective TrmD inhibitors in the series of carboxamide derivatives of thienopyrimidines became a background for further modification of the similar structures aimed at the development of promising antibacterial agents. As part of this research, we carried out the construction of heterocyclic hybrids bearing the moieties of thieno[2,3-d]pyrimidine and benzimidazole starting from 3,5-dimethyl-4-oxo-2-thioxo-1H-thieno[2,3-d]pyrimidine-6-carboxylic acid, which was used as the pivotal intermediate. The hybrid molecule of 6-(1H-benzimidazol-2-yl)-3,5-dimethyl-2-thioxo-1H-thieno[2,3-d]pyrimidin-4-one prepared via condensation of the carboxylic acid with ortho-phenylenediamine was further alkylated with aryl/hetaryl chloroacetamides and benzyl chloride to produce the series of S-alkyl derivatives. The results of molecular docking studies for the obtained series of S-alkyl benzimidazole-thienopyrimidines showed their high affinity to the TrmD isolated from the P. aeruginosa. The results of antimicrobial activity screening revealed the antimicrobial properties for all of the studied molecules against both Gram-positive and Gram-negative bacteria and the Candida albicans fungal strain. The highest antimicrobial activity was determined for 2-{[6-(1H-benzimidazol-2-yl)-3,5-dimethyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl]thio}-N-(4-isopropylphenyl)acetamide, which also had the highest affinity to the TrmD inhibitorβs binding site according to the docking studies results