scholarly journals Metal Complexes as DNA Synthesis and/or Repair Inhibitors: Anticancer and Antimicrobial Agents

2021 ◽  
Vol 03 (04) ◽  
pp. e164-e182
Author(s):  
Mpho Phehello Ngoepe ◽  
Hadley S. Clayton
Keyword(s):  
Dna Synthesis ◽  
Metal Complexes ◽  
Density Functional ◽  
Antimicrobial Agents ◽  
Human Life ◽  
Protein Docking ◽  
Microbial Infection ◽  
Preclinical Development ◽  
In Silico Studies

AbstractMedicinal inorganic chemistry involving the utilization of metal-based compounds as therapeutics has become a field showing distinct promise. DNA and RNA are ideal drug targets for therapeutic intervention in the case of various diseases, such as cancer and microbial infection. Metals play a vital role in medicine, with at least 10 metals known to be essential for human life and a further 46 nonessential metals having been involved in drug therapies and diagnosis. These metal-based complexes interact with DNA in various ways, and are often delivered as prodrugs which undergo activation in vivo. Metal complexes cause DNA crosslinking, leading to the inhibition of DNA synthesis and repair. In this review, the various interactions of metal complexes with DNA nucleic acids, as well as the underlying mechanism of action, were highlighted. Furthermore, we also discussed various tools used to investigate the interaction between metal complexes and the DNA. The tools included in vitro techniques such as spectroscopy and electrophoresis, and in silico studies such as protein docking and density-functional theory that are highlighted for preclinical development.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

Synthesis, Antimicrobial Evaluation and In silico Studies of Novel 2,4- disubstituted-1,3-thiazole Derivatives

2018 ◽  
Vol 16 (2) ◽  
pp. 160-173 ◽  
Author(s):  
Mir Mohammad Masood ◽  
Mohammad Irfan ◽  
Shadab Alam ◽  
Phool Hasan ◽  
Aarfa Queen ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bacterial Strains ◽  
Thiazole Derivatives ◽  
Standard Drug ◽  
Hek 293 ◽  
In Silico Studies

Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds showed moderate to potent antibacterial activity (IC50 = 13.7-90.8 μg/ml). </P><P> Methods: In the antifungal screening, compound (4c) displayed potent antifungal activity (IC50 = 26.5 &#181;g/ml) against Candida tropicalis comparable to the standard drug, fluconazole (IC50 = 10.5 &#181;g/ml). Based on in vitro antimicrobial results, compounds 2f, 4c and 4e were selected for further pharmacological investigations. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed non-toxic nature of the selected compounds (2f, 4c and 4e). To ascertain their possible mode of action, docking studies with the lead inhibitors (2f, 4c and 4e) were performed using crystal structure coordinates of bacterial methionine aminopeptidases (MetAPs), an enzyme involved in bacterial protein synthesis and maturation. Results: The results of in vitro and in silico studies provide a rationale for selected compounds (2f, 4c and 4e) to be carried forward for further structural modifications and structure-activity relationship (SAR) studies against these bacterial infections. Conclusion: The study suggested binding with one or more key amino acid residues in the active site of Streptococcus pneumoniae MetAP (SpMetAP) and Escherichia coli MetAP (EcMetAP). In silico physicochemical properties using QikProp confirmed their drug likeliness.

scholarly journals Synthesis, characterization, in-vitro antimicrobial properties, molecular docking and DFT studies of 3-{(E)-[(4,6-dimethylpyrimidin-2-yl)imino]methyl} naphthalen-2-ol and Heteroleptic Mn(II), Co(II), Ni(II) and Zn(II) complexes

2018 ◽  
Vol 16 (1) ◽  
pp. 184-200 ◽  
Author(s):  
Festus Chioma ◽  
Anthony C. Ekennia ◽  
Aderoju A. Osowole ◽  
Sunday N. Okafor ◽  
Collins U. Ibeji ◽  
...  
Keyword(s):  
Schiff Base ◽  
Molecular Docking ◽  
Metal Complexes ◽  
Drug Targets ◽  
Density Functional ◽  
Radical Scavenging ◽  
Antimicrobial Properties ◽  
Density Functional Theory Calculations ◽  
Elemental Analyses

AbstractHeteroleptic divalent metal complexes [M(L) (bipy)(Y)]•nH2O (where M = Mn, Co, Ni, and Zn; L = Schiff base; bipy = 2,2’-bipyridine; Y = OAc and n = 0, 1) have been synthesized from pyrimidine Schiff base ligand 3-{(E)-[(4,6-dimethylpyrimidin-2-yl)imino]methyl} naphthalen-2-ol, 2,2’-bipyridine and metal(II) acetate salts. The Schiff base and its complexes were characterized by analytical (CHN elemental analyses, solubility, melting point, conductivity) measurements, spectral (IR, UV-vis, 1H and 13C-NMR and MS) and magnetometry. The elemental analyses, Uv-vis spectra and room temperature magnetic moment data provide evidence of six coordinated octahedral geometry for the complexes. The metal complexes’ low molar conductivity values in dimethylsulphoxide suggested that they were non-ionic in nature. The compounds displayed moderate to good antimicrobial and antifungal activities against S. aureus, P. aeruginosa, E. coli, B. cereus, P. mirabilis, K. oxytoca, A. niger, A. flevus and R. Stolonifer. The compounds also exhibited good antioxidant potentials with ferrous ion chelation and, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assays. Molecular docking studies showed a good interaction with drug targets used. The structural and electronic properties of complexes were further confirmed by density functional theory calculations.

scholarly journals Synthesis, Molecular Docking, MEP and SAR Analysis, ADME-Tox Predictions, and Antimicrobial Evaluation of Novel Mono- and Tetra-Alkylated Pyrazole and Triazole Ligands

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Y. Kaddouri ◽  
B. Bouchal ◽  
F. Abrigach ◽  
M. El Kodadi ◽  
M. Bellaoui ◽  
...  
Keyword(s):  
Heterocyclic Compounds ◽  
Antimicrobial Agents ◽  
Antibacterial Activities ◽  
Protein Docking ◽  
Bacterial Strains ◽  
Lead Compounds ◽  
Antimicrobial Evaluation ◽  
Pharmaceutical Industries ◽  
Sar Analysis

Newly synthesized compounds of N-alkylated heterocyclic compounds were prepared by condensation of amine with alcohol which undergoes a reaction of SN2. These newly synthesized derivatives were characterized by spectral analysis. The objective is to prepare new potent nontoxic antimicrobial agents which are easy to synthesize and could be scaled up in pharmaceutical industries. Thirteen new heterocyclic compounds containing a pyrazole moiety were synthesized with good yields (29.79 to 99.6%) and were characterized by FTIR, 1H NMR, 13C NMR, and CG-MS techniques. The compounds were divided into two series—monoalkylated compounds (1–11) and tetra-alkylated compounds (12 and 13)—and then evaluated for their in vitro antifungal and antibacterial activities against several fungal and bacterial strains. None of the monoalkylated compounds had antibacterial or antifungal activity. However, the two tetra-alkylated pyrazole ligands displayed strong antibacterial potential. Moreover, compound 12 was more potent against all tested bacterial strains than compound 13. Interestingly, compounds 12 and 13 acted as weak antifungal agents against Saccharomyces cerevisiae. ADME-Tox studies suggested that compounds 12 and 13 exhibit better toxicity profiles than the commercial antibiotic streptomycin. MEP studies suggested that compounds 12 and 13 have the same charge locations but differ in their values which are due to the condensed geometry of compound 13 that make it more polarizable than compound 12. Of particular interest, these different MEPs were evident in ligand protein docking, suggesting that compound 12 has better affinity with MGL enzyme than compound 13. All these findings suggested that these novel compounds represent promising antibacterial lead compounds.

In Vitro and In Silico Studies of Quinoline-2-Carbaldehyde Hydrazone Derivatives as Potent Antimicrobial Agents

2020 ◽  
pp. 1-17
Author(s):  
Ismail Celik ◽  
Meryem Erol ◽  
Mustafa Orhan Puskullu ◽  
Ebru Uzunhisarcikli ◽  
Ufuk Ince ◽  
...  
Keyword(s):  
In Silico ◽  
Antimicrobial Agents ◽  
In Silico Studies

scholarly journals Novel Zinc(II) Complexes of Heterocyclic Ligands as Antimicrobial Agents: Synthesis, Characterisation, and Antimicrobial Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ramesh S. Yamgar ◽  
Y. Nivid ◽  
Satish Nalawade ◽  
Mustapha Mandewale ◽  
R. G. Atram ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Schiff Base ◽  
Metal Complexes ◽  
Antimicrobial Agents ◽  
Spectroscopic Techniques ◽  
Schiff Base Ligands ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
Antimicrobial Studies

The synthesis and antimicrobial activity of novel Zn(II) metal complexes derived from three novel heterocyclic Schiff base ligands 8-[(Z)-{[3-(N-methylamino)propyl]imino}methyl]-7-hydroxy-4-methyl-2H-chromen-2-one, 2-[(E)-{[4-(1H-1,2,4-triazol-1-ylmethyl)phenyl]imino}methyl]phenol, and (4S)-4-{4-[(E)-(2-hydroxybenzylidene)amino]benzyl}-1,3-oxazolidin-2-one have been described. These Schiff base ligands and metal complexes are characterised by spectroscopic techniques. According to these data, we propose an octahedral geometry to all the metal complexes. Antimicrobial activity of the Schiff base ligand and its metal complexes was studied against Gram negative bacteria:E. coliandPseudomonas fluorescens, Gram positive bacteria:Staphylococcus aureus,and also against fungi, that is,C. albicansandA. niger. Some of the metal complexes show significant antifungal activity (MIC < 0.2 μg/mL). The “in vitro” data has identified [Zn(NMAPIMHMC)2]·2H2O, [Zn(TMPIMP)2]·2H2O, and [Zn(HBABO)2]·2H2O as potential therapeutic antifungal agents againstC. albicansandA. niger.

scholarly journals Piperazine-substituted derivatives of favipiravir for Nipah virus inhibition: What do in silico studies unravel?

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Raju Lipin ◽  
Anantha Krishnan Dhanabalan ◽  
Krishnasamy Gunasekaran ◽  
Rajadurai Vijay Solomon
Keyword(s):  
In Silico ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Nipah Virus ◽  
New Drugs ◽  
Structure Property ◽  
Binding Ability ◽  
Computational Screening ◽  
In Silico Studies

AbstractFavipiravir is found to show excellent in-vitro inhibition activity against Nipah virus. To explore the structure–property relationship of Favipiravir, in silico designing of a series of piperazine substituted Favipiravir derivatives are attempted and computational screening has been done to evaluate its bimolecular interactions with Nipah virus. The geometrical features of all the molecules have been addressed from Density Functional Theory calculations. Chemical reactivity descriptor analysis was carried out to understand various reactivity parameters. The drug-likeness properties were estimated by a detailed ADMET study. The binding ability and the mode of binding of these derivatives into the Nipah virus are obtained from molecular docking studies. Our calculations show greater binding ability for the designed inhibitors compared to that of the experimentally reported molecule. Overall, the present work proves to offers new insights and guidelines for synthetic chemists to develop new drugs using piperazine substituted Favipiravir in the treatment of Nipah virus.

scholarly journals Synthesis, characterization, synergistic antimicrobial properties and molecular docking of sugar modified uridine derivatives

2021 ◽  
Vol 32 (1) ◽  
pp. 6-21
Author(s):  
Jannatul Maowa ◽  
Asraful Alam ◽  
Kazi M. Rana ◽  
Sujan Dey ◽  
Anowar Hosen ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Density Functional ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Docking Study ◽  
Bacterial Strains ◽  
Molecular Docking Study ◽  
Antibacterial And Antifungal Activities

Abstract Nucleosides and their analogues are an important, well-established class of clinically useful medicinal agents that exhibit antiviral and anticancer activity. Thus, our research group has focused on the synthesis of new nucleoside derivatives that could be tested for their broad-spectrum biological activity. In this study, two new series of nucleoside derivatives were synthesized from uridine (1) through facile two-step reactions using the direct acylation method, affording 5’-O-acyl uridine derivatives in good yields. The isolated uridine analogs were further transformed into two series of 2’,3’-di-O-acyl derivatives bearing a wide variety of functionalities in a single molecular framework to evaluate their antimicrobial activity. The new synthesized compounds were characterized through physicochemical, elemental and spectroscopic analysis, and all were screened for their in vitro antimicrobial activity against selected human and plant pathogenic strains. The test compounds revealed moderate to good antibacterial and antifungal activities and were more effective against fungal phytopathogens than against bacterial strains, while many of them exhibited better antimicrobial activity than standard antibiotics. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests against all microorganisms were also conducted for five compounds based on their activity (6, 11, 13, 16, and 17). In addition, all the derivatives were optimized using density functional theory (DFT) B3LYP/6-31g+(d,p) calculations to elucidate their thermal and molecular orbital properties. A molecular docking study was performed using the human protein 5WS1 to predict their binding affinity and modes, and ADMET and SwissADME calculations confirmed the improved pharmacokinetic properties of the compounds. Besides, structure–activity relationship (SAR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) studies were also performed. Thus, the improvement of the bioactivity of these compounds is expected to significantly contribute to the design of more antimicrobial agents for therapeutic use in the future.

scholarly journals Synthesis, characterization and biological activity of new Ni(II), Pd(II) and Cr(III) complex compounds with chlorhexidine

2018 ◽  
Vol 83 (3) ◽  
pp. 271-284 ◽  
Author(s):  
Mădălina Mihalache ◽  
Ticuţa Negreanu-Pîrjol ◽  
Florea Dumitraşcu ◽  
Constantin Drăghici ◽  
Mirela Călinescu
Keyword(s):  
Antimicrobial Activity ◽  
Antioxidant Activity ◽  
Metal Complexes ◽  
Coordination Compounds ◽  
Antimicrobial Agents ◽  
Antioxidant Activities ◽  
Complex Compounds ◽  
Gram Negative Bacteria ◽  
Gram Negative

Six new coordination compounds of Ni(II), Pd(II) and Cr(III) with chlorhexidine, 1,1?-hexamethylenebis[5-(4-chlorophenyl)biguanide], were prepared, characterized and examined for their potential as antimicrobial agents, as well as for their antioxidant activity. The metal complexes correspond to the formulas: [Ni(CHX)]Cl2?2H2O, [Ni(CHX)]Br2?2H2O, [Ni(CHX)](CH3COO)2?C2H5OH, [Pd(CHX)][PdCl4]?2H2O, [Pd(CHX)](CH3COO)2 and [Cr(CHX)Cl2](CH3COO), where CHX = chlorhexidine. Investigations on the in vitro antimicrobial activity of the complexes indicated that all have high activity against the tested bacteria, but are less active against fungi. Among the six complexes, those of Pd(II) showed the highest antibacterial activity, [Pd(CHX)][PdCl4]?2H2O being more active against Gram-positive and Gram-negative bacteria than chlorhexidine diacetate. The antioxidant activity of the metal complexes was investigated by photochemiluminescence and the results showed that the palladium( II) complexes have high antioxidant activities.

scholarly journals Antidiarrheal, antimicrobial and antioxidant potentials of methanol extract of Colocasia gigantea Hook. f. leaves: evidenced from in vivo and in vitro studies along with computer-aided approaches

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Safaet Alam ◽  
Mohammad A. Rashid ◽  
Md. Moklesur Rahman Sarker ◽  
Nazim Uddin Emon ◽  
Mohammad Arman ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Castor Oil ◽  
Antimicrobial Agents ◽  
Methanol Extract ◽  
Control Group ◽  
Soluble Extract ◽  
Molecular Docking Study ◽  
In Silico Studies

Abstract Background Colocasia gigantea, locally named as kochu is well-known due to its various healing power. This research is to investigate the antidiarrheal, antimicrobial and antioxidant possibilities of the methanol soluble extract of Colocasia gigantea. Methods The antidiarrheal investigation was performed by using in vivo castor oil-induced diarrheal method whereas in vitro antimicrobial and antioxidant investigation have been implemented by disc diffusion and DPPH scavenging method respectively. Moreover, in silico studies were followed by molecular docking analysis of several secondary metabolites that were appraised with Schrödinger-Maestro v11.1 and Biovia Discovery Studio. Results The induction of plant extract (200 and 400 mg/kg, b.w, p.o) has minimized the castor oil mediated diarrhea by 16.96% (p < 0.01) and 38.89% (p < 0.001) respectively compared to control group. The methanol extract of C. gigantea showed mild sensitivity against almost all the tested strains but it shows high consistency of phenolic content and yielded 67.68 μg/mL of IC50 value in the DPPH test. In the PASS prediction, selected isolated compounds have demonstrated significant antidiarrheal and antimicrobial activity following the Lipinski drug rules which have ascertained efficacy with the compounds in molecular docking study. Conclusion The results of this scientific research reflects that the methanol soluble extract of C. gigantea is safe and may provide possibilities of alleviation of diarrhea along with being a potential wellspring of antioxidant and antimicrobial agents which can be considered as an alternate source for exploration of new medicinal products in near future.

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