Project description:Our main interest is the characterization of compounds to support the development of alternatives to currently marketed drugs that are losing effectiveness due to the development of resistance. Schiff bases are promising biologically interesting compounds having a wide range of pharmaceutical properties, including anti-inflammatory, antipyretic, and antimicrobial activities, among others. In this work, we have synthesized 12 Schiff base derivatives of 4-aminoantipyrine. In vitro antimicrobial, antioxidant, and cytotoxicity properties are analyzed, as well as in silico predictive adsorption, distribution, metabolism, and excretion (ADME) and bioactivity scores. Results identify two potential Schiff bases: one effective against E. faecalis and the other with antioxidant activity. Both have reasonable ADME scores and provides a scaffold for developing more effective compounds in the future. Initial studies are usually limited to laboratory in vitro approaches, and following these initial studies, much research is needed before a drug can reach the clinic. Nevertheless, these laboratory approaches are mandatory and constitute a first filter to discriminate among potential drug candidates and chemical compounds that should be discarded.
Project description:Metal complexes have been widely used for applications in the chemical and physical sciences due to their unique electronic and stereochemical properties. For decades the use of metal complexes for medicinal applications has been postulated and demonstrated. The distinct characteristics of metal complexes, including their molecular geometries (that are not readily accessed by organic molecules), as well as their ligand exchange, redox, catalytic, and photophysical reactions, give these compounds the potential to interact and react with biomolecules in unique ways and by distinct mechanisms of action. Herein, the potential of metal complexes to act as components bioactive therapeutic compounds is discussed.
Project description:In the era of acquired microbial resistance (AMR), resulting in the ineffectiveness of antibiotics is of keen interest for researchers in current scenarios. Ten novel metal complexes of gemifloxacin have been synthesized by reacting it with essential and trace elements in a 2:1 ratio predetermined conducto-metrically. As these metals are either present in the body or co-administered as metallic supplements can alter the level of antibiotics. Therefore, Metal complexes of Gemifloxacin, an important member of the fluoroquinolone family, were synthesized. The possible coordination of gemifloxacin with these metals has been proposed by the electronic and elemental data obtained through molar conductance, elemental analysis, and spectroscopic techniques like ultraviolet-visible (UV-Vis), infrared (IR), and proton-nuclear magnetic resonance (1H NMR) studies. In the light of these studies, the monoanionic bidentate ligand behavior of gemifloxacin in complexation with metals has been revealed. For in-vitro microbial studies, these newly synthesized complexes were tested against eleven different bacteria including Gram + ve and Gram -ve organisms, and one fungal strain. The results were compared with the parent drug by applying ANOVA through SPSS software version 22. Therefore, it has been found that among all synthesized metal complexes, the G-M01 complex exhibits increased activity against B. subtilis, P. mirabilis, E. coli, K. pneumonia, and C. freundii. Complex G-M02, G-M03, G-M04, and G-M10 show more pronounced activity than Gemifloxacin against S. aureus and M. luteus. Moreover, the binding orientations of the synthesized metal complexes into the binding site of the urease enzyme revealed that all the docked metal complexes oriented away from the Ni bi-center, and the inactivation of urease is due to their interaction with entrance flap residues.
Project description:A sustainable synthesis of interesting glycine betaine derivatives from cyclic 3°-amines viz. N-methyl morpholine (NMM), N-methyl piperidine (NMP), and 1,4-diazabicyclo[2.2.2]octane (DABCO) with numerous aryl diazoacetates 1 in water and under blue LED is reported. Generally, 3°-amines and metal carbenoids (from diazoacetates with transition metal catalysts) provide C-H insertion at the α-position of the amines. Computational comparison of the metal carbenoid with the singlet carbene (metal free and generated under blue LED) realized the difference in reactivity. Next, experimental results corroborated the preliminary findings. The products were isolated either by precipitation of the solid or gel-like final products from the aqueous reaction mixture without any chromatographic purification. The reaction mechanism was realized by control experiments. These compounds exhibit selective bactericidal properties against Gram-positive S. aureus, induce lipid droplets (LDs) formation in HePG2 cells and single crystal X-ray diffraction study of their halogenated analogs reveal interesting Hal … Hal contacts.
Project description:DFT calculations have been carried out for coordinatively saturated neutral and charged carbonyl complexes [M(CO) n ] q where M is a metal atom of groups 2-10. The model compounds M(CO)2 (M = Ca, Sr, Ba) and the experimentally observed [Ba(CO)]+ were also studied. The bonding situation has been analyzed with a variety of charge and energy partitioning approaches. It is shown that the Dewar-Chatt-Duncanson model in terms of M ← CO σ-donation and M → CO π-backdonation is a valid approach to explain the M-CO bonds and the trend of the CO stretching frequencies. The carbonyl ligands of the neutral complexes carry a negative charge, and the polarity of the M-CO bonds increases for the less electronegative metals, which is particularly strong for the group 4 and group 2 atoms. The NBO method delivers an unrealistic charge distribution in the carbonyl complexes, while the AIM approach gives physically reasonable partial charges that are consistent with the EDA-NOCV calculations and with the trend of the C-O stretching frequencies. The AdNDP method provides delocalized MOs which are very useful models for the carbonyl complexes. Deep insight into the nature of the metal-CO bonds and quantitative information about the strength of the [M] ← (CO)8 σ-donation and [M(d)] → (CO)8 π-backdonation visualized by the deformation densities are provided by the EDA-NOCV method. The large polarity of the M-CO π orbitals toward the CO end in the alkaline earth octacarbonyls M(CO)8 (M = Ca, Sr, Ba) leads to small values for the delocalization indices δ(M-C) and δ(M···O) and significant overlap between adjacent CO groups, but the origin of the charge migration and the associated red-shift of the C-O stretching frequencies is the [M(d)] → (CO)8 π-backdonation. The heavier alkaline earth metals calcium, strontium and barium use their s/d valence orbitals for covalent bonding. They are therefore to be assigned to the transition metals.
Project description:In this Minireview, we highlight recent advances in the design of transition metal complexes for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT), and discuss the challenges and opportunities for the translation of such agents into clinical use. New designs for light-activated transition metal complexes offer photoactivatable prodrugs with novel targeted mechanisms of action. Light irradiation can provide spatial and temporal control of drug activation, increasing selectivity and reducing side-effects. The photophysical and photochemical properties of transition metal complexes can be controlled by the appropriate choice of the metal, its oxidation state, the number and types of ligands, and the coordination geometry.
Project description:We have investigated the molecular geometries of a series of dicoordinated d(10)-transition-metal complexes ML2 (M=Co(-), Rh(-), Ir(-), Ni, Pd, Pt, Cu(+), Ag(+), Au(+); L=NH3, PH3, CO) using relativistic density functional theory (DFT) at ZORA-BLYP/TZ2P. Not all complexes have the expected linear ligand-metal-ligand (L-M-L) angle: this angle varies from 180° to 128.6° as a function of the metal as well as the ligands. Our main objective is to present a detailed explanation why ML2 complexes can become bent. To this end, we have analyzed the bonding mechanism in ML2 as a function of the L-M-L angle using quantitative Kohn-Sham molecular orbital (MO) theory in combination with an energy decomposition analysis (EDA) scheme. The origin of bent L-M-L structures is π backdonation. In situations of strong π backdonation, smaller angles increase the overlap of the ligand's acceptor orbital with a higher-energy donor orbital on the metal-ligand fragment, and therefore favor π backdonation, resulting in additional stabilization. The angle of the complexes thus depends on the balance between this additional stabilization and increased steric repulsion that occurs as the complexes are bent.
Project description:In the present research work, four new heterocyclic Schiff base ligands (1–4) were synthesized by the condensation of 4-(4-amino-5-mercapto-4H-1,2,4-triazol-3-yl)phenol with salicylaldehyde derivatives in 1:1 molar ratio. The synthesized Schiff base ligands were allowed for complexation with Co(II), Ni(II), Cu(II), Zn(II) metal ions. The structure of the newly synthesized compounds (1–20) was elucidated with the help of various spectral and physicochemical techniques. Spectroscopic data confirm the tridentate nature of ligands which coordinate to the metal via deprotonated oxygen, azomethine nitrogen and thiol sulphur. Conductivity data showed the non-electrolytic nature of complexes. Furthermore, the synthesized compounds were evaluated for their in-vitro antimicrobial activity against four pathogenic bacterial strains and two pathogenic fungal strains. The observed results of microbial activity reveals that compound 3 and its complexes (13–16) were found most potent against the pathogenic strains. In addition, the anticancer activity of all the synthesized compounds was evaluated against human carcinoma cell lines i.e. HCT-116, DU145 and A549 using MTT assay. Among the tested compounds 12, 19, and 20 were found to show promising potency against the cancer cell lines. To rationalize the preferred modes of interaction of most potent compounds with the active site of human EGFR protein (PDB id: 5XGM), molecular docking studies were performed. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11164-021-04621-5.
Project description:Indole is an important element of many natural and synthetic molecules with significant biological activity. Nonetheless, the co-presence of transitional metals in organic scaffold may represent an important factor in the development of effective medicinal agents. This review covers some of the latest and most relevant achievements in the biological and pharmacological activity of important indole-containing metal complexes in the area of drug discovery.
Project description:The increasing threat of antimicrobial resistance to all currently available therapeutic agents has urged the development of novel antimicrobials. In this context, a series of new benzoylthiourea derivatives substituted with one or more fluorine atoms and with the trifluoromethyl group have been tested, synthesized, and characterized by IR, NMR, CHNS and crystal X-ray diffraction. The molecular docking has provided information regarding the binding affinity and the orientation of the new compounds to Escherichia coli DNA gyrase B. The docking score predicted the antimicrobial activity of the studied compounds, especially against E. coli, which was further demonstrated experimentally against planktonic and biofilm embedded bacterial and fungal cells. The compounds bearing one fluorine atom on the phenyl ring have shown the best antibacterial effect, while those with three fluorine atoms exhibited the most intensive antifungal activity. All tested compounds exhibited antibiofilm activity, correlated with the trifluoromethyl substituent, most favorable in para position.