scholarly journals Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

2021 ◽  
Vol 72 (1) ◽  
pp. 79-95
Author(s):  
Awwad Abdoh Radwan ◽  
Fares Kaed Aanazi ◽  
Mohammed Al-Agamy ◽  
Gamal Mohammad Mahrous
Keyword(s):  
Histidine Kinase ◽  
In Silico ◽  
Binding Mode ◽  
Antibacterial Activities ◽  
Hydroxy Ketone ◽  
Spectroscopic Techniques ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Chemical Structures

Abstract Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated in vitro and by in silico modeling. The compounds were more active against Gram-positive bacteria, Staphylococcus aureus (MIC = 0.026–0.226 mmol L−1) and Bacillus subtilis (MIC = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (MIC = 0.817–7.393 mmol L–1). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (1b) was found as active as imipenem against S. aureus (MIC = 0.026 mmol L–1). In silico docking of the compounds in the binding sites of a homology modeled structure of S. aureus histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of 1b is consistent with its highest docking score values against S. aureus histidine kinase.

scholarly journals In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

2006 ◽  
Vol 50 (6) ◽  
pp. 2261-2264 ◽  
Author(s):  
Hee-Soo Park ◽  
Hyun-Joo Kim ◽  
Min-Jung Seol ◽  
Dong-Rack Choi ◽  
Eung-Chil Choi ◽  
...  
Keyword(s):  
Antibacterial Activities ◽  
The Other ◽  
Vitro Activity ◽  
Gram Negative Bacteria ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

scholarly journals In Vitro and In Vivo Antibacterial Activities of OPC-20011, a Novel Parenteral Broad-Spectrum 2-Oxaisocephem Antibiotic

1998 ◽  
Vol 42 (11) ◽  
pp. 2943-2949 ◽  
Author(s):  
Makoto Matsumoto ◽  
Hisashi Tamaoka ◽  
Hiroshi Ishikawa ◽  
Mikio Kikuchi
Keyword(s):  
Serum Proteins ◽  
Systemic Infection ◽  
Antibacterial Activities ◽  
Gram Negative Bacteria ◽  
Murine Models ◽  
Penicillin Binding Protein ◽  
Gram Positive ◽  
Gram Positive Bacteria

ABSTRACT OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae: MICs at which 90% of the isolates were inhibited were 6.25, 6.25, and 0.05 μg/ml, respectively. Its activity is due to a high affinity of the penicillin-binding protein 2′ in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef. Against gram-negative bacteria, OPC-20011 also showed antibacterial activities similar to those of ceftazidime. The in vivo activities of OPC-20011 were comparable to or greater than those of reference compounds in murine models of systemic infection caused by gram-positive and -negative pathogens. OPC-20011 was up to 10 times as effective as vancomycin against MRSA infections in mice. This better in vivo efficacy is probably due to the bactericidal activity of OPC-20011, while vancomycin showed bacteriostatic activity against MRSA. OPC-20011 produced a significant decrease of viable counts in lung tissue at a dose of 2.5 mg/kg of body weight, an efficacy similar to that of ampicillin at a dose of 10 to 20 mg/kg on an experimental murine model of respiratory tract infection caused by non-ampicillin-susceptibleS. pneumoniae T-0005. The better therapeutic efficacy of OPC-20011 was considered to be due to its potent antibacterial activity and low affinity for serum proteins of experimental animals (29% in mice and 6.4% in rats).

scholarly journals Synthesis andIn VitroAntibacterial Activity of New 2-(1-Methyl-4-nitro-1H-imidazol-5-ylsulfonyl)-1,3,4-thiadiazoles

2011 ◽  
Vol 8 (3) ◽  
pp. 1120-1123 ◽  
Author(s):  
Bahram Letafat ◽  
Negar Mohammadhosseini ◽  
Ali Asadipour ◽  
Alireza Foroumadi
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Antibacterial Activities ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Agar Dilution

In the present study we report the synthesis and antibacterial activity of a new series 2-(1-methyl-4-nitro-1H-imidazol-5-ylsulfonyl)-1,3,4-thiadiazoles (6a-c). Compounds6a-cwere testedin vitroby the conventional agar dilution method against a panel of microorganisms including gram-negative and gram-positive bacteria. Compound6bwith 5-(5-nitrofuran-2-yl)-residue on 1,3,4-thiadiazole scaffold have shown promising antibacterial activities against gram-positive bacteria includingStaphylococcus aureus, Staphylococcus epidermidisandBacillus subtilis.

scholarly journals Synthesis and Pharmacological Evaluation of Some New 2-Phenyl benzimidazoles Derivatives and their Schiff's Bases

2009 ◽  
Vol 6 (s1) ◽  
pp. S342-S346 ◽  
Author(s):  
Y. S. Chhonker ◽  
B. Veenu ◽  
S. R. Hasim ◽  
Niranjan Kaushik ◽  
Devendra Kumar ◽  
...  
Keyword(s):  
Antimicrobial Activities ◽  
Benzimidazole Derivatives ◽  
Spectroscopic Techniques ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
H Nmr ◽  
Ir Spectroscopic

Some new 2- phenyl benzimidazole derivatives were synthesised by cyclocondensation with appropriate reagents. The compounds synthesised were identified by1H NMR, FAB Mass and FT-IR spectroscopic techniques. All compounds studied in this work were screened for theirin vitroantimicrobial activities against the standard strains:Staphylococcus aureusATCC - 25923, ATCC - 441 andBacillus subtilisATCC- 6633 as gram positive,Escherichia coliATCC - 11775 andPseudomonas aeruginosaATCC 10145 as gram negative bacteria. Some of the compounds inhibited the growth of gram-positive bacteria (B. subtilisandS. aureus) at MIC values between 25 and 200 mg/mL. Some of the compounds exhibit antimicrobial activity against gram negative bacteria (E. coliandP. Aeruginosa) MIC values between 25 and 200 mg/mL.

scholarly journals Antibacterial and Anticancer Properties of New Fluoroquinolones

2019 ◽  
Vol 32 (2) ◽  
pp. 427-434
Author(s):  
Maha R. Al Rimawi ◽  
Yusuf M. Al-Hiari ◽  
Amal G. Al-Bakri ◽  
Sanaa K. Bardaweel
Keyword(s):  
Antibacterial Agents ◽  
Spectroscopic Techniques ◽  
Cell Culture System ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Anticancer Properties ◽  
Gram Positive Bacteria ◽  
Good Antibacterial Activity ◽  
Weak Activity

Fluoroquinolones are clinically successful antibacterial agents. In this work a series of novel 7-substituted anilino-8-nitrofluoroquinolone esters (3-9), acids (10-16) and 8-amino reduced derivatives (17-23) of the later compounds were successfully prepared and characterized using spectroscopic techniques. All the compounds tested (10-23) showed good antibacterial activity against both Gram-positive and Gram- negative standard bacterial strains. Interestingly, 8-amino reduced derivatives (17-22) were more active against both standard strains than their 8-nitro acid analogues (10-15). Moreover, some targeted compounds have shown reasonable activity mainly against resistant gram positive bacteria. In particular compounds 10, 12 and 16 displayed a potent activity against methicillin resistant S. aureus (MRSA) with MIC values of 4.7, 2.3 and 1.2 μg/mL, respectively. Lipophilicity could be a plausible explanation of such higher activity against the gram positive resistant strain (MRSA). Biological screening of cytotoxic activity against five cancer cell lines using an in vitro cell culture system was achieved for all tested compounds. These derivatives have shown weak activity for most of them. Interestingly, more lipophilic nitroacids (10-15) were more active than their analogous reduced acids (17-22).

scholarly journals Synthesis, Antibacterial Activities, Mode of Action and Acute Toxicity Studies of New Oxazolidinone-Fluoroquinolone Hybrids

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1641 ◽  
Author(s):  
Liu ◽  
Shao ◽  
Li ◽  
Cui ◽  
Li ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Mode Of Action ◽  
Bacterial Resistance ◽  
Antibacterial Activities ◽  
Oral Toxicity ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Synthetic Hybrids ◽  
Drug Resistant Strains

To combat bacterial resistance, a series of new oxazolidinone-fluoroquinolone hybrids have been synthesized and characterized. All synthetic hybrids were preliminarily evaluated for their in vitro antibacterial activities against 6 standard strains and 3 clinical isolates. The majority of hybrids displayed excellent activities against Gram-positive bacteria, but limited activities against Gram-negative bacteria. Hybrids OBP-4 and OBP-5 were found to be the most promising compounds. Further, in vitro antibacterial activities, mode of action and acute toxicity in mice of hybrids OBP-4 and OBP-5 were investigated. Hybrids OBP-4 and OBP-5 exhibited potent activities against Gram-positive bacteria, including drug-resistant strains. Correspondingly, studies on the mode of action of hybrids OBP-4 and OBP-5 indicated a strong inhibitory activity on protein synthesis by binding the active site of 50S subunit, but a weak inhibitory action on DNA synthesis. In addition, LD50 values of hybrids OBP-4 and OBP-5 in the acute oral toxicity were larger than 2000 mg/kg, suggesting a good safety profile.

scholarly journals 1,3,4-Oxadiazole N-Mannich Bases: Synthesis, Antimicrobial, and Anti-Proliferative Activities

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2110
Author(s):  
Lamya H. Al-Wahaibi ◽  
Ahmed A. B. Mohamed ◽  
Samar S. Tawfik ◽  
Hanan M. Hassan ◽  
Ali A. El-Emam
Keyword(s):  
Proliferative Activity ◽  
Pathogenic Fungus ◽  
Antibacterial Activities ◽  
Mannich Bases ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Primary Aromatic Amines ◽  
Hct 116 ◽  
Breast Cancer Mcf7 Cell

The reaction of 5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thione 3 with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding N-Mannich bases 3-arylaminomethyl-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 4a–l or 3-[(4-substituted piperazin-1-yl)methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 5a–d, respectively. The in vitro inhibitory activity of compounds 4a–l and 5a–d was assessed against pathogenic Gram-positive, Gram-negative bacteria, and the yeast-like pathogenic fungus Candida albicans. The piperazinomethyl derivatives 5c and 5d displayed broad-spectrum antibacterial activities the minimal inhibitory concentration (MIC) 0.5–8 μg/mL) and compounds 4j, 4l, 5a, and 5b showed potent activity against the tested Gram-positive bacteria. In addition, the anti-proliferative activity of the compounds was evaluated against prostate cancer (PC3), human colorectal cancer (HCT-116), human hepatocellular carcinoma (HePG-2), human epithelioid carcinoma (HeLa), and human breast cancer (MCF7) cell lines. The optimum anti-proliferative activity was attained by compounds 4l, 5a, 5c, and 5d.

Indane-1,3-diones: as potential and selective α-glucosidase inhibitors, their synthesis, in vitro and in silico studies.

2020 ◽  
Vol 16 ◽  
Author(s):  
Asma Mukhtar ◽  
Shazia Shah ◽  
Kanwal ◽  
Shehryar Hameed ◽  
Khalid Mohammed Khan ◽  
...  
Keyword(s):  
In Silico ◽  
Binding Mode ◽  
Docking Studies ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
In Silico Docking ◽  
In Silico Studies ◽  
Synthetic Molecules ◽  
Ic50 Values

Background: Diabetes mellitus is one the most chronic metabolic disorder. Since past few years our research group had synthesized and evaluated libraries of heterocyclic compounds against α and β-glucosidase enzymes and found encouraging results. The current study comprises of evaluation of indane-1,3-dione as antidiabetic agents based on our previously reported results obtained from closely related moiety isatin and its derivatives. Objective: A library of twenty three indane-1,3-dione derivatives (1-23) was synthesized and evaluated for α and βglucosidase inhibitions. Moreover, in silico docking studies were carried out to investigate the putative binding mode of selected compounds with the target enzyme. Method: The indane-1,3-dione derivatives (1-23) were synthesized by Knoevenagel condensation of different substituted benzaldehydes with indane-1,3-dione under basic condition. The structures of synthetic molecules were deduced by using different spectroscopic techniques including 1H-, 13C-NMR, EI-MS, and CHN analysis. Compounds (1-23) were evaluated for α and β-glucosidase inhibitions by adopting the literature protocols. Result: Off twenty three, eleven compounds displayed good to moderate activity against α-glucosidase enzyme, nonetheless, all compounds exhibited less than 50% inhibition against β-glucosidase enzyme. Compounds 1, 14, and 23 displayed good activity against α-glucosidase enzyme with IC50 values of 2.80 ± 0.11, 0.76 ± 0.01, and 2.17 ± 0.18 µM, respectively. The results have shown that these compounds have selectively inhibited the α-glucosidase enzyme. The in silico docking studies also supported the above results and showed different types of interactions of synthetic molecules with the active site of enzyme. Conclusion: The compounds 1, 14, and 23 have shown good inhibition against α-glucosidase and may potentially serve as lead for the development of new therapeutic representatives.

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