Synthesis, structure and properties potential biologically active N-aryl-2,2-disubstituted succinimides

У оквиру овог рада, са циљем испитивања утицаја структуре на биолошку ативност, први пут су синтетисане три различите серије једињења деривата сукцинимида (пиролидин-2,5-дионa), и то: N-(3- и 4-супституисани фенил)-2-етил-2- метилсукцинимиди, N-(3- и 4-супституисани фенил)-2-фенил-2- метилсукцинимиди и N-(3- и 4-супституисани фенил)-2-(4-хлорфенил)-2-метилсукцинимиди. Свих 34 једињења су синтетисана према модификованим поступцима из литературе, а структура и чистоћа су потврђена применом одговарајућих спектроскопских метода. Ефекти солватације растварача различитих поларности на електронска својства деривата N-арил-2,2-дисупституисаних сукцинимида су проучавани снимањем UV-Vis апсорпционих спектара у опсегу таласних дужина 200 ̶400 nm. Урађени су квантнохемијски прорачуни, коришћењем програмског пакета Gaussian 09 применом DFT методе. У циљу проналажења најстабилнијих конформера, урађена је конформациона анализа. Одређена је мапа молекулског електростатичког потенцијала деривата и анализа енергија граничних молекуларних орбитала (HOMO и LUMO), као и енергетска разлика између њих, применом B3LYP и М06-2Х/6-311++G(d,p) методе. У наставку истраживања урађена је процена потенцијалне биолошке активности проучаваних једињења. Експериментално је одређена антимикробна активност синтетизованих деривата сукцинимида методом микродилуције, на осам бактеријских врста и осам гљивичних врста.In this paper, three different series of compounds of succinimide derivatives (pyrrolidine-2,5-dione) were synthesized for the first time to investigate the effect of the structure on biological activity: N-(3- and 4-substituted phenyl)-2-ethyl-2-methylsuccinimides, N-(3- and 4-substituted phenyl)-2-phenyl-2-methylsuccinimides and N-(3- and 4-substituted phenyl)-2-(4-chlorophenyl)-2-methylsuccinimides. All 34 compounds were synthesized according to modified literature procedures, and the structure and purity were confirmed using appropriate spectroscopic methods. The effects of the solvation of solvents of different polarities on the electronic properties of N-aryl-2,2-disubstituted succinimide were studied by recording UV-Vis absorption spectra in the wavelength range of 200-400 nm. Quantum-chemical calculations were made using the Gaussian 09 software package using the DFT method. In order to find the most stable conformers, a conformational analysis was made. A map of the molecular electrostatic potential of the derivatives and the analysis of the energy of Frontier Molecular Orbitals (HOMO and LUMO), as well as the energy difference between them, was determined using the B3LYP and M06-2H / 6-311 ++ G (d, p) methods. In the continuation of the research, an assessment was made of the potential biological activity of the compounds studied. The antimicrobial activity of the synthesized succinimide derivatives was experimentally determined by microdilution method, eight bacterial species and eight fungal species.Experimental antimicrobial activity was determined by microdilution method

Spectroscopic and quantum chemical elucidation of newly synthesized 1-aryl-3-methyl-3-phenylpyrrolidine-2,5-diones as potential anticonvulsant agents

Novel succinimide derivatives were synthesized from 3-methyl-3-phenylsuccinic acid and substituted anilines under solvent-free conditions by using microwave irradiation. All obtained compounds were characterized by ultraviolet (UV), Fourier-transform infrared (FT-IR), H-1 and C-13 nuclear magnetic resonance (NMR) spectroscopy as well as by elemental analysis. The influence of the substituent electronic effects on spectroscopic data was analyzed by applying the Hammett equation. Moreover, a detailed interpretation and comparison of experimentally obtained and theoretically calculated FT-IR, UV and NMR spectra was performed. Density functional theory (DFT) calculated data of the investigated succinimides were obtained and analyzed in order to determine their structural, spectroscopic and electronic properties. Furthermore, ADMET factor profiling and in-silico prediction of potential biological activities of novel succinimide derivatives have been performed

Synthesis, structure and properties potential biologically active N-aryl-2,2-disubstituted succinimides

У оквиру овог рада, са циљем испитивања утицаја структуре на биолошку ативност, први пут су синтетисане три различите серије једињења деривата сукцинимида (пиролидин-2,5-дионa), и то: N-(3- и 4-супституисани фенил)-2-етил-2- метилсукцинимиди, N-(3- и 4-супституисани фенил)-2-фенил-2- метилсукцинимиди и N-(3- и 4-супституисани фенил)-2-(4-хлорфенил)-2-метилсукцинимиди. Свих 34 једињења су синтетисана према модификованим поступцима из литературе, а структура и чистоћа су потврђена применом одговарајућих спектроскопских метода. Ефекти солватације растварача различитих поларности на електронска својства деривата N-арил-2,2-дисупституисаних сукцинимида су проучавани снимањем UV-Vis апсорпционих спектара у опсегу таласних дужина 200 ̶400 nm. Урађени су квантнохемијски прорачуни, коришћењем програмског пакета Gaussian 09 применом DFT методе. У циљу проналажења најстабилнијих конформера, урађена је конформациона анализа. Одређена је мапа молекулског електростатичког потенцијала деривата и анализа енергија граничних молекуларних орбитала (HOMO и LUMO), као и енергетска разлика између њих, применом B3LYP и М06-2Х/6-311++G(d,p) методе. У наставку истраживања урађена је процена потенцијалне биолошке активности проучаваних једињења. Експериментално је одређена антимикробна активност синтетизованих деривата сукцинимида методом микродилуције, на осам бактеријских врста и осам гљивичних врста.In this paper, three different series of compounds of succinimide derivatives (pyrrolidine-2,5-dione) were synthesized for the first time to investigate the effect of the structure on biological activity: N-(3- and 4-substituted phenyl)-2-ethyl-2-methylsuccinimides, N-(3- and 4-substituted phenyl)-2-phenyl-2-methylsuccinimides and N-(3- and 4-substituted phenyl)-2-(4-chlorophenyl)-2-methylsuccinimides. All 34 compounds were synthesized according to modified literature procedures, and the structure and purity were confirmed using appropriate spectroscopic methods. The effects of the solvation of solvents of different polarities on the electronic properties of N-aryl-2,2-disubstituted succinimide were studied by recording UV-Vis absorption spectra in the wavelength range of 200-400 nm. Quantum-chemical calculations were made using the Gaussian 09 software package using the DFT method. In order to find the most stable conformers, a conformational analysis was made. A map of the molecular electrostatic potential of the derivatives and the analysis of the energy of Frontier Molecular Orbitals (HOMO and LUMO), as well as the energy difference between them, was determined using the B3LYP and M06-2H / 6-311 ++ G (d, p) methods. In the continuation of the research, an assessment was made of the potential biological activity of the compounds studied. The antimicrobial activity of the synthesized succinimide derivatives was experimentally determined by microdilution method, eight bacterial species and eight fungal species.Experimental antimicrobial activity was determined by microdilution method

Synthesis, antimicrobial activity and quantum chemical investigation of novel succinimide derivatives

In the present study, twelve new 1-aryl-3-ethyl-3-methylpyrrolidine-2,5-diones were synthesized and their structures were characterized by FT-IR, H-1 NMR, C-13 NMR spectroscopy and elemental analysis. In the final step of synthetic rout, condensation between corresponding succinic acid and substituted anilines has been improved using the microwave irradiation. Significantly higher yields compared to conventional condensation have been observed. The preliminary biological results indicated that some of the synthesized compounds showed promising in vitro antifungal activities towards several test fungi. 1-(4-Bromophenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione (8) exhibited significant in vitro inhibitory activities against broad spectra of fungus, and on the basis of obtained data, the investigated bromo derivative has to be observed as novel potential fungicide. The density functional theory (DFT) calculations have been performed in order to study the structure-activity relationship (SAR) of the investigated molecules. In order to prediction of the chemical activity of the molecule, the molecular electrostatic potential (MEP) map was analyzed for the optimized geometry of 1-phenyl-3-ethyl-3-methylpyrrolidine-2,5-dione (4) and 1-(4-bromophenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione (8)

Telomerase stability and evaluation of real-time telomeric repeat amplification protocol

Telomerase is RNA directed polymerase which acts as reverse transcriptase based on its own RNA component. It is considered to be involved in the pathology of many diseases and is recognized as a potential biomarker. The aims were to determine the sample storage conditions and the time frame for samples analysis, then to prove reliability of enzyme activity measurement with real-time telomeric repeat amplification protocol (TRAP) and to evaluate the suitable standard samples for telomerase activity measurements. Samples used for stability and freeze-thaw study were peripheral blood leukocytes, obtained from apparently healthy persons, patients with diagnosed cancer and cell lines. Telomerase activity was measured using TRAP method, while standard evaluation was done using nuclear magnetic resonance (NMR) technique. Storage at -20 degrees C preserved telomerase activity in samples from cancer patients for at least 14 days (21.46 +/- 0.135 versus 21.84 +/- 0.357, p = .756), while samples obtained from healthy persons should be stored at -80 degrees C. We observed significant decrease of telomerase activity at freeze thaw cycle 5 in cancer patients' samples (21.46 +/- 0.135 versus 23.09 +/- 0.316, p lt .05), and in healthy persons' ones already at cycle 3 (22.74 +/- 0.107 versus 24.85 +/- 0.151, p lt .05). Telomerase activity from cell lines samples showed overall greater stability regarding the storage period and freeze-thaw cycles and it was considered for standard sample, which was confirmed by NMR analysis. Telomerase enzyme had adequate stability while efficacy, linearity, and reproducibility of TRAP method were acceptable for bio-analytical methods. All this indicated that telomerase could be a reliable biomarker