4-Substituted thieno[2,3-d]pyrimidines as potent antibacterial agents: Rational design, microwave-assisted synthesis, biological evaluation and molecular docking studies. 2017

Rupinder K Gill, and Harpreet Singh, and Tilak Raj, and Anuradha Sharma, and Gagandeep Singh, and Jitender Bariwal
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.

In an attempt to discover a new class of antibacterial agents with improved efficacy and to overcome the drug-resistant problems, some novel 4-substituted thieno[2,3-d]pyrimidines have been synthesized via microwave-assisted methodology and evaluated for their in vitro antibacterial activity against various pathogenic bacterial strains. Compounds 12b and 13c showed the promising inhibitory potencies against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli with MICs ranging from 2 to 10 μg/ml. Compound 13c was also found to be highly potent against methicillin-resistant S. aureus (MRSA) with MIC value of 4 μg/ml. Docking simulation studies have been performed to unravel the mode of action and association study indicate the binding of potent compounds with DHPS enzyme. In silico ADME studies suggest the drug-like characteristics of the potent compounds.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D008856 Microscopy, Fluorescence Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye. Fluorescence Microscopy,Immunofluorescence Microscopy,Microscopy, Immunofluorescence,Fluorescence Microscopies,Immunofluorescence Microscopies,Microscopies, Fluorescence,Microscopies, Immunofluorescence
D008872 Microwaves That portion of the electromagnetic spectrum from the UHF (ultrahigh frequency) radio waves and extending into the INFRARED RAYS frequencies. EHF Waves,Extremely High Frequency Radio Waves,Micro Wave,Micro Waves,Ultrahigh Frequency Waves,Microwave Radiation,EHF Wave,Micro Waves,Microwave,Microwave Radiations,Radiation, Microwave,Ultrahigh Frequency Wave,Wave, EHF,Wave, Micro,Wave, Ultrahigh Frequency,Waves, Micro
D011550 Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection. Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D004094 Dihydropteroate Synthase An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. EC 2.5.1.15. Dihydropteroate Pyrophosphorylase,Dihydropteroate Synthetase,Pyrophosphorylase, Dihydropteroate,Synthase, Dihydropteroate,Synthetase, Dihydropteroate
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001412 Bacillus subtilis A species of gram-positive bacteria that is a common soil and water saprophyte. Natto Bacteria,Bacillus subtilis (natto),Bacillus subtilis subsp. natto,Bacillus subtilis var. natto
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial

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