CONFORMATIONAL ANALYSIS IN 18-MEMBERED MACROLIDE ANTIBIOTICS BASED ON MOLECULAR MECHANICS.

Conformational analysis of macrolides with 18-ring membered has been carried out using molecular mechanics calculations and molecular dynamics. A high conformational mobility of no complexed macrocycles has been obtained and an important stereoselectivity has been observed for the complexed macrocycles. For 18d macrolide, which was presented by a privileged conformer with 20.1% without complex, was populated with 50.1% in presence of Fe(CO)3. For the most privileged conformer geometry; the α,β-unsaturated ester group has an s-cis conformation with a torsion angle φ1: O19-C2-C3-C4 = 14.5° for macrocycle 18d macrolide and φ1: O19-C2-C3-C4 = 25.0° for 18s macrolide. The diene group has an s-trans conformation with a torsion angle φ2:C11-C12-C13-C14 = 169.4° for 18d macrolide and φ2:C10-C11-C12-C13 = 179.5° for 18s macrolide.  L’analyse conformationnelle des macrolides à 18 chaînons a été réalisée par des calculs de mécanique moléculaire et de dynamique moléculaire. Une mobilité conformationnelle élevée a été obtenue pour les macrocycles non complexés et une stéréosélectivité importante a été observé pour les macrocycles complexés. Pour le macrolide 18d, qui a été présenté par un conformère privilégié avec 20.1% sans complexe, est devenu 50.1% en présence de Fe(CO)3 Pour la géométrie du conformère le plus privilégiée; le système d’ester α,β-insaturé, a une conformation s-cis avec un angle de torsion φ1 : O19-C2-C3-C4 = 14.5° pour le macrolide 18d et φ1 : O19-C2-C3-C4 = 25.0° pour le macrolide 18s. Le système diène a une conformation s-trans avec un angle de torsion φ2 : C11-C12-C13-C14 = 169.4° pour macrolide 18d et φ2:C10-C11-C12-C13 = 179.5° pour macrolide 18s

Strength and durability of low-impact environmental self-compacting concrete incorporating waste marble powder

This research studies the effect of waste marble powder (WMP) as substitute of Portland cement on strength and durability of self-compacting concrete (SCC) in order to produce SCC with reduced impact environmental. For this purpose, five mixtures were designed in which four mixtures contained WMP at substitution levels of 5, 10, 15, 20%, and mixture included only the Portland cement as control mix. The realized tests are compressive strength at 3, 7 and 28 days, water capillary absorption, water absorption by immersion and sulfate attack. The results show a reduction in the compressive strength with increasing WMP content. The use of WMP was found to increase both of the water capillary absorption and water absorption by immersion. SCC containing WMP subjected to magnesium sulfate attack presented a lower expansion and higher resistance to sulfate aggressions

Effect of limestone powder as a partial replacement of crushed quarry sand on properties of self-compacting repair mortars

Self-compacting repair mortars (SCRM) are particularly desired for the rehabilitation and repair of reinforced concrete structures. The properties of SCRM can be improved by using chemical, mineral, polymer and fiber additives. In limestone quarries, considerable quantities of limestone fine powder are obtained during the process of crushing rock. These fine powders are being collected and their utilization is a big problem from the aspects of disposal, environmental pollution and health hazards. The introduction of limestone powder as cement and sand replacement present interesting possibilities to reduce the cement cost production, CO2 emission and the conservation of natural resources. The effects of limestone powder content in crushed sand on the properties of SCRM are not studied. An experimental study was undertaken to find out the effect of limestone powder content on fresh and hardened properties of SCRM. SCRM mixtures were prepared using crushed sand partially replaced with limestone powder at varying percentages up to 30%. Results indicate that the limestone powder as sand replacement significantly improves the fresh and hardened properties of SCRM with a content ranging from 10 to 15%. The use of limestone powder in repair mortar and concrete application would offer technical, economical and environmental advantages for concrete producers.Self-compacting repair mortars (SCRM) are particularly desired for the rehabilitation and repair of reinforced concrete structures. The properties of SCRM can be improved by using chemical, mineral, polymer and fiber additives. In limestone quarries, considerable quantities of limestone fine powder are obtained during the process of crushing rock. These fine powders are being collected and their utilization is a big problem from the aspects of disposal, environmental pollution and health hazards. The introduction of limestone powder as cement and sand replacement present interesting possibilities to reduce the cement cost production, CO2 emission and the conservation of natural resources. The effects of limestone powder content in crushed sand on the properties of SCRM are not studied. An experimental study was undertaken to find out the effect of limestone powder content on fresh and hardened properties of SCRM. SCRM mixtures were prepared using crushed sand partially replaced with limestone powder at varying percentages up to 30%. Results indicate that the limestone powder as sand replacement significantly improves the fresh and hardened properties of SCRM with a content ranging from 10 to 15%. The use of limestone powder in repair mortar and concrete application would offer technical, economical and environmental advantages for concrete producers.Self-compacting repair mortars (SCRM) are particularly desired for the rehabilitation and repair of reinforced concrete structures. The properties of SCRM can be improved by using chemical, mineral, polymer and fiber additives. In limestone quarries, considerable quantities of limestone fine powder are obtained during the process of crushing rock. These fine powders are being collected and their utilization is a big problem from the aspects of disposal, environmental pollution and health hazards. The introduction of limestone powder as cement and sand replacement present interesting possibilities to reduce the cement cost production, CO2 emission and the conservation of natural resources. The effects of limestone powder content in crushed sand on the properties of SCRM are not studied. An experimental study was undertaken to find out the effect of limestone powder content on fresh and hardened properties of SCRM. SCRM mixtures were prepared using crushed sand partially replaced with limestone powder at varying percentages up to 30%. Results indicate that the limestone powder as sand replacement significantly improves the fresh and hardened properties of SCRM with a content ranging from 10 to 15%. The use of limestone powder in repair mortar and concrete application would offer technical, economical and environmental advantages for concrete producers

Combined Pharmacophore Modeling, 3D-QSAR, Molecular Docking and Molecular Dynamics Study on Indolyl-aryl-sulfone Derivatives as New HIV1 Inhibitors

The present study deals with the in silico of 45 indolyl-aryl-sulfones known as anti-HIV1. The data were collected from recent previously reported inhibitors and divided into a sub-set of 33 compounds as the training set and the remaining 12 compounds were kept in the test set. The selected pharmacophore–ADRRR–yielded a statistically significant 3D-QSAR model containing high confidence scores (R2 = 0.930, Q2 = 0.848, and RMSE = 0.460). The predictive power of the established pharmacophore model was validated with an external test (r2 = 0.848). A systematic virtual screening workflow shows an enrichment factor and has revealed a high predictive power. Then the model was used to screen the filtered PubChem database mapping all chemical features of model pharmacophore. The recognized hits were further assessed by in silico ADMET studies. Molecular dynamics also used to explore the stability of obtained complexes. Finally, these selected compounds are probably to become a good lead molecule for the development of effective anti-HIV-1 drugs

Effect of limestone powder as a partial replacement of crushed quarry sand on properties of self-compacting repair mortars

Self-compacting repair mortars (SCRM) are particularly desired for the rehabilitation and repair of reinforced concrete structures. The properties of SCRM can be improved by using chemical, mineral, polymer and fiber additives. In limestone quarries, considerable quantities of limestone fine powder are obtained during the process of crushing rock. These fine powders are being collected and their utilization is a big problem from the aspects of disposal, environmental pollution and health hazards. The introduction of limestone powder as cement and sand replacement present interesting possibilities to reduce the cement cost production, CO2 emission and the conservation of natural resources. The effects of limestone powder content in crushed sand on the properties of SCRM are not studied. An experimental study was undertaken to find out the effect of limestone powder content on fresh and hardened properties of SCRM. SCRM mixtures were prepared using crushed sand partially replaced with limestone powder at varying percentages up to 30%. Results indicate that the limestone powder as sand replacement significantly improves the fresh and hardened properties of SCRM with a content ranging from 10 to 15%. The use of limestone powder in repair mortar and concrete application would offer technical, economical and environmental advantages for concrete producers

In silico evaluation of Molecular Structure, Vibrational Spectra and Substitution Effect of Hydantoin

ABSTRACT In this study the Molecular geometry optimization, vibrational frequencies, energy gaps, net charges, dipole moments and heats of formation Hydantoin at the ground state, in present work, we have been calculated and performed by using the Molecular Mechanics, PM3, ab initio/HF and DFT/B3LYP methods basis set in order to obtain optimized geometrical parameters are in good agreement with experimental values. Comparison of the obtained fundamental vibrational frequencies of hydantoin result by DFT/B3LYP (6-311G++ (d, p)) method, are in a close agreement with the experimental data. Ab initio/HF with 6-31G basis set was used to investigate the effects of a variety of substituants (methyl ,dimethyl, trimethyl ,and chloride ,dichloride ,trichloride ) on the electronic properties of hydantoin derivatives. Detailed vibrational wave number shifts and vibrational mode analyses were reported

Quantitative Structure-Activity Relationship Modeling of Detoxication Properties of Some 1,2-Dithiole-3-Thione Derivatives

Quantitative Structure-Activity Relationship (QSAR) studies have been performed on nineteen molecules of 1,2-dithiole-3-thione analogues. The compounds used are the potent inducers of enzymes involved in the maintenance of reduced glutathione pools as well as phase-2 enzymes important to electrophile detoxication. A multiple linear regression (MLR) procedure was used to design the relationships between molecular descriptor and detoxication properties of the 1,2-dithiole-3-thione derivatives. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based of the following descriptors: qS2, qC3, qC5, qS6, DM, Pol, log P, MV, SAG, HE and EHOMO for the specific activity of quinone reductase; qS1, qS2, qC3, qC4, qC5, qS6, DM, Pol, logP, MV, SAG, HE and EHOMO for the production of growth hormone. To confirm the predictive power of the models, an external set of molecules was used. High correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the derived QSAR models

In silico investigation applied in physical, chemical properties and vibrational analysis of 1.3.4-thiadiazole derivatives

International audienceThe equilibrium geometries of 1,3,4-thiadiazole derivatives have been determined and analyzed at DFT level employing B3LYP/6-31G(d) basis set. The molecular electrostatic potential surface (MESP) that reveals centers of reactivity of the molecule and substitution effects of the molecular system have been studied using the HSAB principle (Hard Soft Acid and Base).Results such us, fundamental vibrational modes, H-1 NMR isotropic chemical shifts, frontier orbital energies (HOMO, LUMO), band gap energy, dipole moments, net charges are reported and discussed in terms of reactivity of 1,3,4-thiadiazole derivatives. The HOMO and LUMO analysis were used to elucidate information regarding charge transfer within the molecule. Isotropic chemical shifts were calculated using the Gauge-Independent Atomic Orbital (GIOAO) method. Finally, a comparison between the experimental data and the calculated results appeared a good agreement and show exceptional reactivity

QSAR studies of 1,2,5-thiadiazole derivatives analogues of aceclidine as potent M1 muscarinic agonists

International audienceIn the present study, Quantitative structure-activity relationship (QSAR) study have been performed on twenty molecules of 1,2,5-thiadiazole derivatives. The compounds studied are the analogues of aceclidine as potent M1 muscarinic agonists. A multiple linear regression (MLR) procedure was used to design the relationships between molecular descriptors and biological activity of the 1,2,5- thiadiazole derivatives. The predictivity of the model was estimated by cross-validation with the leave-one-outmethod. Our results suggest a QSAR model based on the following descriptors Log P , HE, Pol, MR, MV, and MW, SAG, and Etotal. High correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the established QSAR models. © 2018 American Scientific Publishers