Ring-opening polymerization of a 2,3-disubstituted oxirane leading to a polyether having a carbonyl-aromatic pi-stacked structure

2-Methoxycarbonyl-3-(3,4-dimethoxyphenyl) oxirane was synthesized and polymerized using a cationic initiator to afford a polymer having a rather stiff, stretched conformation. The side-chain methoxycarbonyl group and 3,4-dimethoxyphenyl group of neighboring monomeric units may form a hetero pi-stacked structure between side-chain carbonyl and aromatic groups which leads to intramolecular charge transfer (ICT) interactions. 2-Ethoxy-carbonyl- 3-phenyloxirane failed in polymerization, leading only to small molecules including cyclic compounds

Stereochemical characterization of methyl trans-3-(3,4-dimethoxyphenyl)glycidate by enantioselective HPLC-CD analysis and TD-DFT calculations

Enantiomerically pure oxiranes are valuable electrophilic, chiral synthons [1] and have been introduced into pharmaceutical applications for the synthesis of biologically active polyethers. Stereochemical characterization plays an important role in medicinal chemistry, since chirality is fundamental in the definition of the activity of several biologically active compounds. Consequently, analytical techniques allowing for the stereochemistry to be fully characterized are receiving increasing attention. The absolute configuration of methyl trans-3-(3,4- dimethoxyphenyl)glycidate (trans-1), a recently synthesized building block for the synthesis of methylated analogues of biologically active polymers from different species of comfrey and bugloss [2], was investigated by means of enantioselective high-performance liquid chromatography hyphenated with a circular dichroism detection system (eHPLC-CD) [3]. A Lux Cellulose-4 and a Lux Cellulose-2 columns were successfully employed for the preparative and analytical enantioresolution of racemic trans-1 [4]. The CD spectra of the enantiomeric fractions of trans-1 were then measured both by off-line analysis after preparative chromatographic separation and by stopped-flow measurements during the eHPLC-CD analysis [3]. This last strategy resulted more reliable, because the risk of degradation of the analyte was drastically reduced. The absolute configuration of each enantiomeric fraction was finally determined by comparison of the experimental CD spectra with quantum mechanical (QM) calculations based on time-dependent density functional theory (TD-DFT). The conformationally-averaged theoretical CD spectrum of (2S,3R)-1 reproduced with a reasonable degree of accuracy the CD spectrum of the first-eluted fraction of trans-1 on the Lux Cellulose-2 column: consequently, a full stereochemical characterization of the enantiomers of trans-1 was achieved and the elution order on Lux Cellulose-2 was determined. [1] H.C. Kolb, M.S. VanNieuwenhze, K.B. Sharpless, Catalytic asymmetric dihydroxylation, Chem. Rev. 94 (1994) 2483\u20132547. [2] V. Barbakadze, L. Gogilashvili, L. Amiranashvili, M. Merlani, K. Mulkijanyan, Novel biologically active phenolic polymers from different species of genera Symphytum and Anchusa (Boraginaceae), J. Chem. Eng. Chem. Res. 1 (2014) 47\u201353. [3] C. Bertucci, D. Tedesco, Advantages of electronic circular dichroism detection for the stereochemical analysis and characterization of drugs and natural products by liquid chromatography, J. Chromatogr. A 1269 (2012) 69\u201381. [4] K. Lomsadze, M. Merlani, V. Barbakadze, T. Farkas, B. Chankvetadze, Enantioseparation of chiral epoxides with polysaccharide-based chiral columns in HPLC, Chromatographia 75 (2012) 839\u2013845

Antimicrobial Activity of Some Steroidal Hydrazones

Twelve steroid based hydrazones were in silico evaluated using computer program PASS as antimicrobial agents. The experimental evaluation revealed that all compounds have low to moderate antibacterial activity against all bacteria tested, except for B. cereus with MIC at a range of 0.37–3.00 mg/mL and MBC at 0.75–6.00 mg/mL. The most potent appeared to be compound 11 with MIC/MBC of 0.75/1.5 mg/mL, respectively. The evaluation of antibacterial activity against three resistant strains MRSA, E. coli and P. aeruginosa demonstrated superior activity of compounds against MRSA compared with ampicillin, which did not show bacteriostatic or bactericidal activities. All compounds exhibited good antifungal activity with MIC of 0.37–1.50 mg/mL and MFC of 1.50–3.00 mg/mL, but with different sensitivity against fungi tested. According to docking studies, 14-alpha demethylase inhibition may be responsible for antifungal activity. Two compounds were evaluated for their antibiofilm activity. Finally, drug-likeness and docking prediction were performed

Antimicrobial Activity of Some Steroidal Hydrazones

Twelve steroid based hydrazones were in silico evaluated using computer program PASS as antimicrobial agents. The experimental evaluation revealed that all compounds have low to moderate antibacterial activity against all bacteria tested, except for B. cereus with MIC at a range of 0.37–3.00 mg/mL and MBC at 0.75–6.00 mg/mL. The most potent appeared to be compound 11 with MIC/MBC of 0.75/1.5 mg/mL, respectively. The evaluation of antibacterial activity against three resistant strains MRSA, E. coli and P. aeruginosa demonstrated superior activity of compounds against MRSA compared with ampicillin, which did not show bacteriostatic or bactericidal activities. All compounds exhibited good antifungal activity with MIC of 0.37–1.50 mg/mL and MFC of 1.50–3.00 mg/mL, but with different sensitivity against fungi tested. According to docking studies, 14-alpha demethylase inhibition may be responsible for antifungal activity. Two compounds were evaluated for their antibiofilm activity. Finally, drug-likeness and docking prediction were performed

Antimicrobial Activity of Catechol-Containing Biopolymer Poly[3-(3,4-dihydroxyphenyl)glyceric Acid] from Different Medicinal Plants of Boraginaceae Family

This study reports the antimicrobial activities of the biopolymers poly[3-(3,4-dihydoxyphenyl)glyceric acid] (PDHPGA) and poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO), extracted from the six plants of Boraginaceae family: Symphytum asperum (SA), S. caucasicum (SC), S. gr and iflorum (SG), Anchusa italica (AI), Cynoglosum officinale (CO), and Borago officinalis (BO) collected in various parts of Georgia. The study revealed that the antibacterial activities were moderate, and biopolymers from only three plants showed activities against all tested bacteria. Biopolymers from CO stems as well as SC and AI did not show any activity except low activity against a resistant P. aeruginosa strain, which was the most resistant among all three resistant strains. On the other hand, the antifungal activity was better compared to the antibacterial activity. Biopolymers from BO stems exhibited the best activities with MIC/MFC at 0.37–1.00 mg/mL and 0.75–1.5 mg/L, respectively, followed by those from SG stems. Biopolymers from SC and AI roots showed antifungal activities against all six fungi, in contrast to the antibacterial activity, while biopolymers from CO stems and SA roots had activities against four fungi and one fungus, respectively. The sugar-based catechol-containing biopolymers from BO stems demonstrated the best activities among all tested biopolymers against T. viride, P. funiculosum, P. cyclpoium var verucosum, and C. albicans (MIC 0.37 mg/mL). In addition, biopolymers from SG stems were half as active against A. fumigatus and T. viride as ketoconazole. Biopolymers from all plant materials except for CO stems showed higher potency than ketoconazole against T. viride. For the first time, it was shown that all plant materials exhibited better activity against C. albicans, one of the most dreadful fungal species

Enzymatic Synthesis and Antimicrobial Activity of Oligomer Analogues of Medicinal Biopolymers from Comfrey and Other Species of the Boraginaceae Family

This study reports the first enzymatic synthesis leading to several oligomer analogues of poly[3-(3,4-dihydroxyphenyl)glyceric acid]. This biopolymer, extracted from plants of the Boraginaceae family has shown a wide spectrum of pharmacological properties, including antimicrobial activity. Enzymatic ring opening polymerization of 2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane (MDBPO) using lipase from Candida rugosa leads to formation of poly[2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane] (PMDBPO), with a degree of polymerization up to 5. Catalytic debenzylation of PMDBPO using H2 on Pd/C yields poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO) without loss in molecular mass. Antibacterial assessment of natural polyethers from different species of Boraginaceae family Symhytum asperum, S. caucasicum,S. grandiflorum, Anchusa italica, Cynoglossum officinale, and synthetic polymers, poly[2-methoxycarbonyl-3-(3,4-dimethoxyphenyl)oxirane (PMDMPO) and PMDHPO, reveals that only the synthetic analogue produced in this study (PMDHPO) exhibits a promising antimicrobial activity against pathogenic strains S.aureus ATCC 25923 and E.coli ATCC 25922 the minimum inhibitory concentration (MIC) being 100 µg/mL

Antimicrobial Activity of Nitrogen-Containing 5-α-Androstane Derivatives: In Silico and Experimental Studies

We evaluated the antimicrobial activity of thirty-one nitrogen-containing 5-α-androstane derivatives in silico using computer program PASS (Prediction of Activity Spectra for Substances) and freely available PASS-based web applications (such as Way2Drug). Antibacterial activity was predicted for 27 out of 31 molecules; antifungal activity was predicted for 25 out of 31 compounds. The results of experiments, which we conducted to study the antimicrobial activity, are in agreement with the predictions. All compounds were found to be active with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values in the range of 0.0005–0.6 mg/mL. The activity of all studied 5-α-androstane derivatives exceeded or was equal to those of Streptomycin and, except for the 3β-hydroxy-17α-aza-d-homo-5α-androstane-17-one, all molecules were more active than Ampicillin. Activity against the resistant strains of E. coli, P. aeruginosa, and methicillin-resistant Staphylococcus aureus was also shown in experiments. Antifungal activity was determined with MIC and MFC (Minimum Fungicidal Concentration) values varying from 0.007 to 0.6 mg/mL. Most of the compounds were found to be more potent than the reference drugs Bifonazole and Ketoconazole. According to the results of docking studies, the putative targets for antibacterial and antifungal activity are UDP-N-acetylenolpyruvoylglucosamine reductase and 14-α-demethylase, respectively. In silico assessments of the acute rodent toxicity and cytotoxicity obtained using GUSAR (General Unrestricted Structure-Activity Relationships) and CLC-Pred (Cell Line Cytotoxicity Predictor) web-services were low for the majority of compounds under study, which contributes to the chances for those compounds to advance in the development

New Caffeic Acid Derivatives as Antimicrobial Agents: Design, Synthesis, Evaluation and Docking.

BACKGROUND Phenolic acids (caffeic-, ferulic and p-coumaric acid) are widely distributed in the plant kingdom and exhibit broad spectrum of biological activities, including antimicrobial activity. OBJECTIVE The goal of this paper is the synthesis of some caffeic acid derivatives selected based on computer-aided predictions and evaluate their in vitro antimicrobial properties against Gram positive and Gram negative bacteria and also a series of fungi. METHODS In silico prediction of biological activity was used to identify the most promising structures for synthesis and biological testing, and the putative mechanisms of their antimicrobial action. The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was studied using microdilution method. RESULTS Twelve tested compounds have shown good antibacterial activity. Five out of twelve tested compounds appeared to be more active than the reference drugs ampicillin and streptomycin. Despite that all compounds exhibited good activity against all bacteria tested, the sensitivity of bacteria towards compounds in general was different. The evaluation of antifungal activity revealed that all compounds were more active than ketoconazole, while seven compounds (2, 3, 4, 5, 7, 8 and 12) appeared to be more active than bifonazole. Docking results indicate that gyrase inhibition is the putative mechanism of antibacterial action while the inhibition of 14α-demethylase may be responsible for antifungal action. Prediction of cytotoxicity by PROTOX showed that compounds are not toxic (LD50 1000-2000 mg/kg). CONCLUSION Thirteen compounds, from which six are new ones, were synthesized, and twelve compounds were tested for antimicrobial activity. The studied compounds appeared to be promising potent and non-toxic antimicrobials, which could be considered as leads for new pharmaceutical agents