scholarly journals Biological Activity, Lipophilicity and Cytotoxicity of Novel 3-Acetyl-2,5-disubstituted-1,3,4-oxadiazolines

2021 ◽  
Vol 22 (24) ◽  
pp. 13669
Author(s):  
Kinga Paruch ◽  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Hordyjewska ◽  
Łukasz Popiołek
Keyword(s):  
Biological Activity ◽  
Normal Cell ◽  
Chemical Structure ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Bactericidal Effect ◽  
Normal Cell Line ◽  
Starting Point ◽  
Good Starting Point ◽  
Staphylococcus Spp

Antibiotic resistance is now a global problem, and the lack of effective antimicrobial agents for the treatment of diseases caused by resistant microbes is increasing. The 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines presented in this article may provide a good starting point for the development of potential new effective antimicrobial agents useful in the treatment of bacterial and fungal infections. Particular attention is drawn to the 1,3,4-oxadiazole derivative marked with the number 29 with 5-nitrofuran-2-yl substituent in its chemical structure. This substance showed a strong bactericidal effect, especially against Staphylococcus spp., and no cytotoxicity to the L929 normal cell line.

scholarly journals Novel 3-Acetyl-2,5-disubstituted-1,3,4-oxadiazolines: Synthesis and Biological Activity

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5844
Author(s):  
Kinga Paruch ◽  
Łukasz Popiołek ◽  
Anna Biernasiuk ◽  
Anna Hordyjewska ◽  
Anna Malm ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Aromatic Aldehydes ◽  
Bactericidal Effect ◽  
In Vitro Assays ◽  
Bacterial Strains ◽  
Stage Synthesis ◽  
Low Cytotoxicity ◽  
Staphylococcus Spp

The aim of our study was the two-stage synthesis of 1,3,4-oxadiazole derivatives. The first step was the synthesis of hydrazide–hydrazones from 3-methyl-4-nitrobenzhydrazide and the corresponding substituted aromatic aldehydes. Then, the synthesized hydrazide–hydrazones were cyclized with acetic anhydride to obtain new 3-acetyl-2,3-disubstituted-1,3,4-oxadiazolines. All of obtained compounds were tested in in vitro assays to establish their potential antimicrobial activity and cytotoxicity. Our results indicated that few of the newly synthesized compounds had some antimicrobial activity, mainly compounds 20 and 37 towards all used reference bacterial strains (except Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa) and fungi. These substances showed a strong or powerful bactericidal effect, especially against Staphylococcus spp. belonging to Gram-positive bacteria. Compound 37 was active against Staphylococcus epidermidis at minimal inhibitory concentration (MIC) = 0.48 µg/mL and was characterized by low cytotoxicity. This compound possessed quinolin-4-yl substituent in the second position of 1,3,4-oxadiazole ring and 3-methyl-4-nitrophenyl in position 5. High effectiveness and safety of these derivatives make them promising candidates as antimicrobial agents. Whereas the compound 20 with the 5-iodofurane substituent in position 2 of the 1,3,4-oxadiazole ring showed the greatest activity against S. epidermidis at MIC = 1.95 µg/mL.

Cytotoxic Effect of Pseudomonas aurogenosa Protease on Cancer Cells

2019 ◽  
Vol 10 (03) ◽  
Author(s):  
Ghanyia J. Shanyoor ◽  
Fatima R. Abdul ◽  
Nehad A. Taher ◽  
Ihsan A. Raheem
Keyword(s):  
Cell Line ◽  
Normal Cell ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Skim Milk ◽  
Exchange Chromatography ◽  
Protease Production ◽  
Normal Cell Line ◽  
Protease Enzyme ◽  
Embryonic Fibroblast

About (20) Pseudomonas rogenosa isolate were experienced for their ability of protease production by calculating the diameter of lysis area after developing on skim milk agar medium (qualitatively ) and the results exhibited that only isolate no (5), was higher isolate for protease making of (26mm) of lysis area. Then, the protein concentration also identified by Bradford method and it was found of 0.16 mg/ ml , then purification was done by using an ion- exchange chromatography with DEAE sephadex G- 100 column and the results showed the presence of 1 peak of enzyme with 50 Kd of molecular weight 2 peaks of other proteins . we tried to investigate the invitro Cytotoxic effect of purified enzyme against two human cancer lines, HeP2 (Human larynx epidermed carcinoma ) , RD ( Rabdo- Sarcoma ) , and one normal cell line Ref ( Rat embryonic fibroblast ) . The cancer and normal cells were treated with different concentrations of protease enzyme ranging from ( 0.05, 0.1, 0.2, 0.4,0.8and 0.16 mg/ml) then incubated for additional 48h at 37C0 and the results showed highest toxicity ( 80.28%) of protease enzyme on RD , moderate cytotoxicity (45.52%) on Hep andslight toxicity ( 37.12% ) on normal cell line (Ref) in a concentration (0.8mg/ml).

Discovery of Antibacterial Agents Inhibiting the Energy-Coupling Factor (ECF) Transporters by Structure-Based Virtual Screening

2020 ◽  
Author(s):  
Eleonora Diamanti ◽  
Inda Setyawati ◽  
Spyridon Bousis ◽  
leticia mojas ◽  
lotteke Swier ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Energy Coupling ◽  
Coupling Factor ◽  
Design Synthesis ◽  
Screening Design ◽  
Starting Point ◽  
Wide Range ◽  
Vitamin Uptake

Here, we report on the virtual screening, design, synthesis and structure–activity relationships (SARs) of the first class of selective, antibacterial agents against the energy-coupling factor (ECF) transporters. The ECF transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. Because of their central role in the metabolism of bacteria and their absence in humans, ECF transporters are novel potential antimicrobial targets to tackle infection. The hit compound’s metabolic and plasma stability, the potency (20, MIC Streptococcus pneumoniae = 2 µg/mL), the absence of cytotoxicity and a lack of resistance development under the conditions tested here suggest that this scaffold may represent a promising starting point for the development of novel antimicrobial agents with an unprecedented mechanism of action.<br>

Heterocycle Compounds with Antimicrobial Activity

2020 ◽  
Vol 26 (8) ◽  
pp. 867-904 ◽  
Author(s):  
Maria Fesatidou ◽  
Anthi Petrou ◽  
Geronikaki Athina
Keyword(s):  
Heterocyclic Compounds ◽  
Bacterial Infections ◽  
Scientific Community ◽  
Antimicrobial Agents ◽  
Fungal Infections ◽  
Biological Activities ◽  
Literature Survey ◽  
New Findings ◽  
Wide Range ◽  
Number Of Microorganisms

Background: Bacterial infections are a growing problem worldwide causing morbidity and mortality mainly in developing countries. Moreover, the increased number of microorganisms, developing multiple resistances to known drugs, due to abuse of antibiotics, is another serious problem. This problem becomes more serious for immunocompromised patients and those who are often disposed to opportunistic fungal infections. Objective: The objective of this manuscript is to give an overview of new findings in the field of antimicrobial agents among five-membered heterocyclic compounds. These heterocyclic compounds especially five-membered attracted the interest of the scientific community not only for their occurrence in nature but also due to their wide range of biological activities. Method: To reach our goal, a literature survey that covers the last decade was performed. Results: As a result, recent data on the biological activity of thiazole, thiazolidinone, benzothiazole and thiadiazole derivatives are mentioned. Conclusion: It should be mentioned that despite the progress in the development of new antimicrobial agents, there is still room for new findings. Thus, research still continues.

Novel 1,2,3-Triazole-functionalized pyrido[3',2':4,5]furo[3,2-d]pyrimidin- 4(3H)-one Derivatives: Synthesis, Anticancer Activity, CoMFA and CoMSIA Studies

2020 ◽  
Vol 17 (12) ◽  
pp. 969-978
Author(s):  
Balakishan Vadla ◽  
Sailu Betala
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Normal Cell ◽  
Rational Design ◽  
Human Cancer ◽  
Strong Basis ◽  
Hek 293 ◽  
Normal Cell Line ◽  
Human Cancer Cell Lines ◽  
Mcf 7

A series of novel triazole functionalized pyrido [3',2':4,5] furo[3,2-d] pyrimidin-4 (3H)-one derivatives 7a-p were prepared from ethyl furo[2,3-b]pyridine-2-carboxylate 3 on reaction with ammonia to afford furo[2,3-b]pyridine-2-carboxamide 4. This compound, on reaction with triethyl orthoformate TEOF, gave compound 5. Compound 5 on propargylation, followed by a reaction with substituted aryl azides under Sharpless reaction conditions, furnished triazole tagged pyrido [3',2':4,5]furo[3,2-d] pyrimidin-4(3H)-one derivatives. All the products 7a-p were screened against four human cancer cell lines, such as HeLa - Cervical cancer (CCL-2), COLO 205- Colon cancer (CCL-222), HepG2- Liver cancer (HB-8065), and MCF7 - Breast cancer (HTB-22) and one normal cell line (HEK 293). Compounds 7b, 7n, 7o and 7p, which showed promising anticancer activity, were identified and found to be non-toxic to normal cell line. Studies for HeLa, COLO205, HepG2, and MCF-7 using CoMFA and CoMSIA were carried out . Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF-7 cell line inhibitors.

Design, Synthesis and In Vitro Anti-Cancer Evaluation of Novel Derivatives of 2-(2-Methyl-1,5-diaryl-1H-pyrrol-3-yl)-2-oxo-N-(pyridin-3- yl)acetamide

2020 ◽  
Vol 16 (3) ◽  
pp. 340-349
Author(s):  
Ebrahim S. Moghadam ◽  
Farhad Saravani ◽  
Ernest Hamel ◽  
Zahra Shahsavari ◽  
Mohsen Alipour ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Peripheral Neuropathy ◽  
Cell Line ◽  
Normal Cell ◽  
Caspase 3 ◽  
Annexin V ◽  
Normal Cell Line ◽  
Anti Cancer ◽  
Mcf 7

Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100 μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: Newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.

Constraints in Adoption ofModern Farm Machines by Tribal Farmers in Ramgarh District of Jharkhand

2019 ◽  
Vol 6 (03) ◽  
Author(s):  
PK SUNDARAM ◽  
BIKASH SARKAR ◽  
UJJWAL KUMAR ◽  
AP ANURAG ◽  
DK RAGHAV ◽  
...  
Keyword(s):  
Cell Line ◽  
Normal Cell ◽  
Human Cancer ◽  
Skim Milk ◽  
Exchange Chromatography ◽  
Protease Production ◽  
Normal Cell Line ◽  
Protease Enzyme ◽  
Tribal Farmers ◽  
Embryonic Fibroblast

About (20) Pseudomonas rogenosa isolate were experienced for their ability of protease production by calculating the diameter of lysis area after developing on skim milk agar medium (qualitatively ) andamp; the results exhibited that only isolate no (5), was higher isolate for protease making of (26mm) of lysis area. Then, the protein concentration also identified by Bradford method andamp; it was found of 0.16 mg/ ml , then purification was done by using an ion- exchange chromatography with DEAE sephadex G- 100 column andamp; the results showed the presence of 1 peak of enzyme with 50 Kd of molecular weight 2 peaks of other proteins . we tried to investigate the invitro Cytotoxic effect of purified enzyme against two human cancer lines, HeP2 (Human larynx epidermed carcinoma ) , RD ( Rabdo- Sarcoma ) , andamp; one normal cell line Ref ( Rat embryonic fibroblast ). The cancer andamp; normal cells were treated with different concentrations of protease enzyme ranging from ( 0.05, 0.1, 0.2, 0.4,0.8andamp; 0.16 mg/ml) then incubated for additional 48h at 37C 0 andamp; the results showed highest toxicity ( 80.28%) of protease enzyme on RD , moderate cytotoxicity (45.52%) on Hep andamp;slight toxicity ( 37.12% )on normal cell line (Ref) in a concentration (0.8mg/ml).

scholarly journals Discovery and Optimization of Selective Inhibitors of Meprin α (Part I)

2021 ◽  
Vol 14 (3) ◽  
pp. 203 ◽  
Author(s):  
Shurong Hou ◽  
Juan Diez ◽  
Chao Wang ◽  
Christoph Becker-Pauly ◽  
Gregg B. Fields ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
De Novo ◽  
Selective Inhibitors ◽  
Preclinical Development ◽  
Starting Point ◽  
Good Starting Point ◽  
Parallel Screening ◽  
Low Cytotoxicity

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in preclinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultrahigh-throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified five selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These selective inhibitors of meprin α provide a good starting point for further optimization.

scholarly journals Advances on the Implementation of Circular Economy Techniques in Rural Areas in Colombia under a Sustainable Development Framework

2021 ◽  
Vol 13 (7) ◽  
pp. 3816
Author(s):  
Javier Rodrigo-Ilarri ◽  
Camilo-A. Vargas-Terranova ◽  
María-Elena Rodrigo-Clavero ◽  
Paula-A. Bustos-Castro
Keyword(s):  
Sustainable Development ◽  
Waste Management ◽  
Circular Economy ◽  
Rural Areas ◽  
Development Framework ◽  
Starting Point ◽  
Management Plans ◽  
Good Starting Point ◽  
Depressed Regions ◽  
First Time

For the first time in the scientific literature, this research shows an analysis of the implementation of circular economy techniques under sustainable development framework in six municipalities with a depressed economy in Colombia. The analysis is based on solid waste data production at a local scale, the valuation of the waste for subsequent recycling, and the identification and quantification of the variables associated with the treatment and final disposal of waste, in accordance with the Colombian regulatory framework. Waste generation data are obtained considering three different scenarios, in which a comparison between the simulated values and those established in the management plans are compared. Important differences have been identified between the waste management programs of each municipality, specifically regarding the components of waste collection, transportation and disposal, participation of environmental reclaimers, and potential use of materials. These differences are fundamentally associated with the different administrative processes considered for each individual municipality. This research is a good starting point for the development of waste management models based on circular economy techniques, through the subsequent implementation of an office tool in depressed regions such as those studied.

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