Syntheses and anti-microbial evaluation of new quinoline scaffold derived pyrimidine derivatives

A series of diversely substituted chalcones derived from a quinoline scaffold, e.g. (E)-3-(2-chloroquinolin-3-yl)-1-(2-hydroxyphenyl) prop-2-en-1-one and its pyrimidine analogues e.g. 2-[2-amino-6-(2-chloroquinolin-3-yl)-5,6-dihydropyrimidin-4-yl]phenols have been prepared by condensation of 2-chloro-3-formyl quinoline with differently substituted 2-hydroxy acetophenones and further treatment with guanidine carbonate. All the newly synthesized compounds have been evaluated for their in vitro growth inhibitory activity against Escherichia coli, Pseudomonas vulgaris, Bacillus subtilis, Staphylococcus aureus, Staphylococcus typhi, Candida albicans, Aspergillus niger and Pseudomonas chrysogenum

Solid supported microwave induced synthesis of imidazole–pyrimidine hybrids: Antimicrobial evaluation and docking study as 14DM-CPY51 inhibitors

As part of our exploration for new antifungal agents, substituted 4,5-diphenyl imidazolyl pyrimidine hybrids were synthesized. A series of substituted ethyl 1,2,3,6-tetrahydro-4-methyl-2-oxo/thioxo-6-phenyl-1-(4,5-diphenyl-1-H-imidazol-2-yl) pyrimidine-5-carboxylates have been studied for their binding active sites of cytochrome P450 14α-sterol demethylase CPY51 enzyme. For comparison, the binding behavior of known 14DM selective (Fluconazole) and non-selective (Clotrimazole, Miconazole, Griesofulvin) drugs has also been studied. Synthesized compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, Salmonella typhi, Pseudomonas aurogenosa and Klebsiella pneumonae and also antifungal activity against the opportunistic pathogens Candida albicans

Computational Evaluation of 2-Phenyl-4H-chromen-4-one Analogues as Antihistamines: Potential Histamine N-Methyltransferase (HMT) Inhibitors

Abnormal release of histamine, which is present in relatively high concentration in the lungs, causes serious allergic vasoconstriction and anaphylactic manifestation in human beings. In mammals, a major pathway of histamine metabolism in the lungs is mediated by histamine N-methyl transferase (HMT) and diamine oxidase. The need to design a strategy of mechanistic computational evaluation of protein-ligand affinity i.e. HMT- 2-phenyl-4H-chromen-4-ones, protein complex binding energy has been established. A library of synthesized 2-phenyl-4H-chromen-4-ones was docked into the active site cavity of target protein, HMT (Pdb: 2aot). The high-resolution crystal structure of HMT complex with the competitive inhibitor N [2 (benzhydryloxy)ethyl] N N-Dimethylamine (Diphenhydramine) revealed a protein with a highly confined binding region that could be targeted in the design of specific anti-histamines. The validation of docking programme by Potential Mean Force was compared with binding energy results of known ligands in the active sites of HMT, diphenhydramine / benadryl, promethazine, cyproheptadine, trimeton / avil etc. All the synthesized chromone derivatives showed comparable negative binding energies pointing towards the fact that these molecules could be potent antihistamines

<span style="font-size:12.0pt;font-family: "Times New Roman";mso-fareast-font-family:"Times New Roman";mso-ansi-language: EN-GB;mso-fareast-language:EN-US;mso-bidi-language:AR-SA" lang="EN-GB">Stereoselective bioreduction of chalcone and β-diketone by <i style="mso-bidi-font-style:normal">Saccharomyces cerevisiae</i> in biphasic solvent system: A mechanistic study</span>

992-1001<span style="font-size:12.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-ansi-language:="" en-gb;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-GB">&nbsp;A mechanistic study of steroselective bio-reduction of chalcones and β-diketones to their corresponding hydroxy derivatives with an effective and versatile biocatalyst <i style="mso-bidi-font-style: normal">i.e. Saccharomyces cerevisiae (Baker’s yeast) in different biphasic solvents systems have been carried out. Maximum bioreduction was observed in pet. ether-water (60% v/v), chloroform-water (60% v/v) for compound (R)-3-(5-chloro-2-hydroxyphenyl)-3-hydroxyl-1-phenylpropane-1-one 2a and (R)-3-(5-methyl-2-hydroxyphenyl)-3-hydroxyl-1-phenylpropane-1-one 2b, respectively while ethanol-water (80%v/v) for 4-chloro-2- ((R, <i style="mso-bidi-font-style: normal">E)-1-hydroxy-3-phenyl allyl) phenol <b style="mso-bidi-font-weight: normal">4a. These biphasic systems are instrumental in integrating bioconversion and product recovery in a single system and shifting the chemical equilibrium to enhance yield and selectivity.</span

Synthesis and antimicrobial activity of 5-(2-aminothiazol-4-yl)-3, 4-dihydro-4-phenyl pyrimidin-2(1<i style="">H</i>)-one

1732-1737A series of hybrid 5-(2-aminothiazol-4-yl)-3,4-dihydro-4-phenyl pyrimidin-2(1H)-ones (ATDPP) are reported. Efficient cyclocondensation of appropriately substituted 5-(2-bromoacetyl)-3,4-dihydro-4-phenylpyrimidine-2(1H)-ones (BADPP) with thiourea in ethanol proceeds in high yield to furnish the corresponding ATDPPs. Dihydropyrimidine carboxylates (DHPMS) and their bromo derivatives are the key substrates for cyclocondensation. The ATDPPS revealed biological activity as antimicrobial and antifungal agents against S. aureus, P. aurogenosa, K. pneumonae and C. albicans.</i

ChemInform Abstract: Experimental and Computational Evaluation of New Quinolinyl Chalcones as Potent Antiplasmodial Agents.

1780-1793 In a search for new antiplasmodial agents, a series of thirty five diversely substituted chalcones derived from a quinoline-chalcone scaffold e.g. (E)-3-(2-chloroquinolin-3-yl)-1-(2-hydroxyphenyl) prop-2-en-1-one / (E)-(2-chloro-6-ethoxyquinolin-3-yl) (2-hydroxyphenyl) prop-2-en-1-one and (2Z)-3-(2-chloroquinolin-3-yl)-1-(2-hydroxyphenyl)-3-iodoprop-2-en-1-one are synthesized and studied. Compounds are prepared via Claisen–Schmidt condensations of 2-chloro-3-formyl quinoline / 2-chloro-6-ethoxy-3-formyl quinoline with appropriately substituted 2-hydroxy acetophenones. All compounds are assayed for their binding in the active sites of Plasmodium falciparum lactate dehydrogenase (pfLDH) enzyme. The quinoline chalcone derivatives showed negative binding energies promising potent pfLDH inhibitory activity. Compounds showing the highest negative binding scores have been studied for their in vitro antimalarial activity against cultured Plasmodium falciparum 3D7 strain. The compounds 2c and 2u have completely inhibited the maturation of parasites at MIC 10 µg/mL and above whereas 3b inhibited 95% maturation of parasites at MIC 50 µg/mL. Additional efforts are being directed towards elaborating these leads towards the discovery and development of new quinolinyl heterocycles as anti-malarial agents. </smarttagtype

Experimental and computational evaluation of new quinolinyl chalcones as potent antiplasmodial agents

1780-1793 In a search for new antiplasmodial agents, a series of thirty five diversely substituted chalcones derived from a quinoline-chalcone scaffold e.g. (E)-3-(2-chloroquinolin-3-yl)-1-(2-hydroxyphenyl) prop-2-en-1-one / (E)-(2-chloro-6-ethoxyquinolin-3-yl) (2-hydroxyphenyl) prop-2-en-1-one and (2Z)-3-(2-chloroquinolin-3-yl)-1-(2-hydroxyphenyl)-3-iodoprop-2-en-1-one are synthesized and studied. Compounds are prepared via Claisen–Schmidt condensations of 2-chloro-3-formyl quinoline / 2-chloro-6-ethoxy-3-formyl quinoline with appropriately substituted 2-hydroxy acetophenones. All compounds are assayed for their binding in the active sites of Plasmodium falciparum lactate dehydrogenase (pfLDH) enzyme. The quinoline chalcone derivatives showed negative binding energies promising potent pfLDH inhibitory activity. Compounds showing the highest negative binding scores have been studied for their in vitro antimalarial activity against cultured Plasmodium falciparum 3D7 strain. The compounds 2c and 2u have completely inhibited the maturation of parasites at MIC 10 µg/mL and above whereas 3b inhibited 95% maturation of parasites at MIC 50 µg/mL. Additional efforts are being directed towards elaborating these leads towards the discovery and development of new quinolinyl heterocycles as anti-malarial agents. </smarttagtype