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*Corresponding Author: Ali Souldozi, Department of Chemistry, Urmia Branch, Islamic Azad University, Urmia, Iran.
Citation: Naeimeh Nazari, Ali Souldozi, (2023), Synthesis and Evaluation of Antibacterial Activity of Novel Disubstituted 1,3,4-Oxadiazoles Derivatives Containing Fluorine Substituent, J, Biotechnology and Bioprocessing, 4(3); DOI: 10.31579/2766-2314/102
Copyright: 2023, Ali Souldozi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 29 May 2023 | Accepted: 07 June 2023 | Published: 15 June 2023
Keywords: N-isocyaniminotriphenylphosphorane; 1,3,4-oxadiazoles; antibacterial activity
In the present study a new series of antibacterial agents (4a-f) was designed, synthesized and evaluated for antibacterial activity against different gram positive (Staphylococcusaureus, Staphylococcus epidermidis, Bacillus cereus) and gram negative (listeria monocytogenes, Escherichia coli, Pseudomonas aeroginosa) bacteria. New derivatives of oxadiazoles were prepared by one-pot reaction of N-isocyanoiminotriphenylphosphorane, carboxylic acid derivatives and 2-pyridinecarboxaldehyde, in the presence of acetonitrile solvent. The broth macro dilution and well agar diffusion methods were used for determination of inhibition zone (IZ) and minimum inhibitory concentration (MIC) during preliminary evaluation of antimicrobial activity. The (MIC) values of tested compounds revealed that all compounds have displayed significant antibacterial activity against Staphylococcusaureus and Staphylococcus epidermidis (with MIC values in the range of 31 to 125µg/mL).
Widespread antibiotic resistance appeared over the last 60 years and generates a serious challenge to the medical pundits. Despite the presence of antibiotics in structural and vaccination programmes, infectious diseases are major causes of morbidity and mortality worldwide. Thus, there is essential need to novel insights into development of drugs with new mechanisms of action. Among the wide variety of heterocycles that have been explored for developing new therapeutic molecules, 1,3,4-oxadiazoles become promising moiety in the structure of drugs [1,2]. 1,3,4-Oxadiazole are known to show antibacterial [3,4], antifungal [5], analgesic [6], anti-inflammator [7,8], antitubercular [9], pesticidal [10]. anti-HIV [11]and anti-cancer [12]. The improvement in activity due to the presence of aromatic moiety in the molecules that increases the lipophilicity and affects the subdividing of molecules into membranes and comfort hydrophobic interactions of the molecules with specific binding sites on either receptor or enzymes is well established [13]. In recent years, a number of new 1,3,4-oxadiazole derivatives as antibacterial agents have been reported. The main modifications of these compounds were focused on triflouromethyl and flourophenyl groups [14]. In this research, we designed and synthesized new series of fluorinated 1,3,4-oxadiazoles derivatives and evaluated there in vitro antibacterial activity against against some pathogenic bacteria.
2.1 Materials and Methods
Chemistry 1H (300.13 MHz) and 13C (75.47 MHz) NMR measurements were recorded on a Bruker 250 spectrometer in CDCl3 with tetramethylsilane as internal standard. IR spectra were measured on a Shimadzu IR-460 spectrometer. Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. N-isocyanoiminotriphenylphosphorane 2 was prepared based on a reported procedure [15,16]. Other starting materials and solvents were obtained from Merck (Germany) and Fluka (Switzerland) and were used without further purification. Flash chromatography columns were prepared from Merck silica gel powder. The structures of the products were deduced from their IR, 1H NMR and 13C NMR spectra.
2.2 General Procedure for the Preparation of products (4a-f)
To a magnetically stirred solution of N-isocyanoiminotriphenylphosphorane (1) (0.302 g, 1 mmol) in CH3CN (8 ml) was added drop-wise a solution of 2(1 mmol) in CH3CN (7 ml) over 15 min. The mixture was stirred for 12 h at room temperature. The solvent was removed under reduced pressure and the viscous residue was purified by flash column chromatography (silica gel; petroleum ether–ethyl acetate (10:3). The solvent was removed under reduced pressure and the products (4a–f) were obtained.
(5-(2-fluorophenyl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol (4a)
White powder, m.p. 122 ºC, yield 74%
IR (KBr) (νmax , Cm-1): 3416, 3064, 2927, 1685, 1609, 1491, 1437, 1191, 1117, 722.
1HNMR (300.13 MHz, CDCl3): δH= 6.24 (s, CH, Aliphatic), 6.63 (s, 1H, OH), 7.31-7.37 (m, 2H, CH, Ar), 7.64-7.67 (m, 1H, CH, Ar), 7.88-7.91 (m, 1H, CH, Ar), 7.93-8.01(m, 1H, CH, Pyridine ring), 8.23-8.26 (m, 1H, CH, Pyridine ring), 8.47-8.51 (m, 1H, CH, Pyridine ring), 8.88-8.93 (m, 1H, CH, Pyridine ring ).
13CNMR (75.467 MHz, CDCl3): δC= 66.7 (CH-OH), 116.8 (1C, d, 2JCF= 22.3 Hz, Ar), 119.4 (1C, d, 2JCF= 10.4 Hz, Ar), 124.4 (1CH, d, 4JCF= 4.1 Hz, C Ar), 131.8 (1CH, d, 3JCF= 1.4 Hz, Ar), 134.6 (1CH, d, 3JCF= 9.0 Hz, Ar), 124.9, 128.4, 137.5, 150.5 (4 CH Pyridine ring), 155.4 and 166.8 (1C, d, 1JCF= 256.8 Hz, Ar), 158.3 (1C, Pyridine ring), 161.9 (1C, oxadiazol ring), 165.1 and 164.1 (1C, d, 3JCF= 22.9 Hz, oxadiazol ring).
(5-(3-fluorophenyl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol (4b)
White powder, m.p. 125 ºC, yield 71%.
IR (KBr) (νmax , Cm-1): 3435 (br), 3055, 2924, 2855, 1677, 1549, 1463, 1370, 1216, 1180, 1091, 998.
1HNMR (300.13 MHz, CDCl3): δH= 6.16 (s, 1H, CH aliphatic), 6.54 (s, 1H, OH), 7.31-7.36 (m, 1H, CH, Ar), 7.54-7.64 (m, 1H, CH, Ar), 7.64-7.67 (m, 1H, CH, Ar), 7.94-7.98 (m, 2H, CH, Ar), 8.01-8.06 (m, 1H, CH, Pyridine ring), 8.46 (d, 1H, 3JHH= 8.1 Hz, CH, Pyridine ring), 8.92-8.93 (m, 1H, CH Pyridine ring).
13CNMR (75.467 MHz, CDCl3): δC= 66.8 (CH-OH), 114.9 (d, 1H, 2JCF= 24.4 Hz, CH Ar), 120.0 (d, 1CH, 2JCF= 21.2 Hz, Ar), 123.7 (d, 1C, 3JFC= 3.4 Hz, Ar), 126.1 (d, 1CH, 4JFC= 3.2 Hz, Ar), 125.7, 128.2, 137.3, 150.2 (4 CH Pyridine ring), 157.7 and 167.5 (d, 1C, 1JFC= 352.2 Hz, Ar), 158.2 (1C, Pyridine ring), 161.7, 166.8 (2C).
(5-(4-fluorophenyl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol (4c)
White powder, m.p. 128 ºC, yield 77%
IR (KBr) (νmax , Cm-1):3406, 3057, 2928, 1677, 1607, 1491, 1438, 1185, 1115, 716.
1HNMR (300.13 MHz, CDCl3): δH= 6.23 (s, CH, Aliphatic), 6.61 (s, 1H, OH), 7.47-7.48 (m, 2H, CH, Ar), 7.64-7.71 (m, 2H, CH, Ar), 7.53-7.55 (m, 1H, CH, Pyridine ring), 7.99-8.04 (m, 1H, CH Ar), 8.42-8.45 (d, 1H,3JHH= 7.5 Hz, CH Ar), 8.89-8.91 (m, 1H, CH Pyridine ring).
13CNMR (75.467 MHz, CDCl3): δC= 67.0 (CH-OH), 115.5 (2CH, d, 2JCF= 22.1 Hz, CH Ar), 132.0 (2CH, d, 3JCF= 9.0 Hz, CH Ar), 162.4 and 167.4 (1C, d, 1JCF= 250.4 Hz, C Ar), 127.4 (1C Ar), 125.7, 128.2, 137.2, 150.2 (4 CH Pyridine ring), 158.2 (1C, Pyridine ring), 161.7, 166.8 (2C).
(5-(3,4-difluorophenyl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol (4d)
White powder, m.p. 140 ºC, yield 81%
IR (KBr) (νmax , Cm-1): 3412, 3062, 2926, 1683, 1601, 1486, 1431, 1185, 1112, 718.
1HNMR (300.13 MHz, CDCl3): δH= 6.20 (s, CH, Aliphatic), 6.61 (s, 1H, OH), 7.46-7,54 (m, 2H, Ar), 7.64-7.71 (m, 1H, Ar), 7.96-8.01 (m, 1H, Pyridine ring), 8.21-8.25 (m, 1H, Pyridine ring), 8.44-8.46 (m, 1H, Pyridine ring), 8.87-8.91 (m, 1H, Pyridine ring).
13CNMR (75.467 MHz, CDCl3): δC= 66.8 (CH-OH), 116.7 (1CH, d, 3JCF= 22.6 Hz, CH Ar), 119.2-120.1 (1CH, d of d, 3JCF= 2.0 Hz, 2JCF= 16.9 Hz, CH Ar), 126.1-126.5 (1CH, d of d, 4JCF= 2.3 Hz, 3JCF= 3.5 Hz, CH Ar), 127.4 (1CH , q, 3JCF= 3.8 Hz, CH Ar), 149.0-149.5 and 155.0-155.5 (1CF, d of d, 2JCF= 12.8 Hz, 1JCF= 257.9 Hz), 145.0-145.6 and 155.0-155.5 (1CF, d of d, 2JCF= 12.8 Hz, 1JCF= 257.9 Hz, CF Arom), 124.7, 128.2, 137.3, 150.2 (4CH, Pyridine ring), 158.3(1C, Pyridine ring), 161.8, 166.8 (2C).
pyridin-2-yl(5-(3-(trifluoromethyl) phenyl)-1,3,4-oxadiazol-2-yl) methanol (4e)
White powder, m.p. 143 ºC, yield 84%
IR (KBr) (νmax , Cm-1): 3408, 3062, 2931, 1678, 1610, 1497, 1442, 1190, 1118, 718.
1HNMR (300.13 MHz, CDCl3): δH= 6.21 (s, CH, Aliphatic), 6.64 (s, 1H, OH), 7.61-7.64 (m, 1H, CH, Ar), 7.81-7.88 (m, 1H, CH, Ar), 8.34-8.38 (m, 2H, CH, Ar), 7.95-7.99 (m, 1H, CH, Pyridine ring), 8.03-8.08 (m, 1H, CH, Pyridine ring), 8.45 (1H, d, 3JHH= 8 Hz, Pyridine ring), 8.94-8.97 (m, 1H, CH, Pyridine ring).
13CNMR (75.467 MHz, CDCl3): δC= 66.9 (CH-OH), 107.4, 118.3, 129.1, 139.9 (1C, q, 1JCF= 272.2 Hz, Ar), 127.3 (1CH, q, 3JCF= 3.8 Hz, Ar), 129.5, 130.8, 132.1, 133.5 (1C, q, 2JCF= 33.2 Hz, Ar), 129.3, 133.5 (2CH, Ar), 130.8 (1C, Ar), 130.5 (1CH, q, 3JCF= 3.8 Hz, Ar), 125 .8, 128.4, 137.4, 150.3 (4 CH, Pyridine ring), 158.4 (1C, Pyridine ring), 161.8, 166.9 (2C, Oxadiazol ring).
pyridin-2-yl(5-(4-(trifluoromethyl) phenyl)-1,3,4-oxadiazol-2-yl) methanol(4f)
White powder, m.p. 146 ºC, yield 85%
IR (KBr) (νmax , Cm-1): 3412, 3071, 2931, 1679, 1610, 1496, 1444, 1189, 1117, 715.
1HNMR (300.13 MHz, CDCl3): δH= 6.22 (s, CH, Aliphatic), 6.62 (s, 1H, OH), 7.88 (2H, d, 3JHH= 8 Hz, Ar), 8.17 (2H, d, 3JHH= 8.0 Hz, Ar), 7.94-8.01(m, 1H, CH, Pyridine ring), 8.03-8.09 (m, 1H, CH, Pyridine ring), 8.47 (1H, d, 3JHH= 8.0 Hz, Pyridine ring), 8.87-8.92 (m, 1H, CH, Pyridine ring).
13CNMR (75.467 MHz, CDCl3): δC= 67.0 (CH-OH), 125.5 (2CH, q, 3JCF= 3.6 Hz, Ar), 130.1 (2CH, Ar), 130.5, 131.9, 133.3, 134.8 (1C, q, 2JCF= 32.2 Hz, Ar), 105.7, 117.8, 129.9, 142.0 (1C, q, 1JCF= 272.6 Hz, Ar), 134.8 (1C, Ar), 125.7, 128.3, 137.2, 150.3 (4 CH Pyridine ring), 158.4 (1C, Pyridine ring), 161.9, 166.9 (2C, Oxadiazol ring).
3.1 Agar well diffusion method
The antibacterial activity of synthesized compounds was investigated against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, listeria monocytogenes ATCC 23074, Pseudomonas aeroginosa ATCC 27853, Bacillus cereus ATCC 11778, Staphylococcus epidermidis ATCC 14990 by agar well diffusion and broth dilution methods [15-16].
The standardization of each bacterial inoculum was done following the following them to Clinical & Laboratory Standards Institute (CLSI) [17]. Briefly, each microorganism after inoculation into Mueller Hinton broth (Merck, Germany) was prepared to turbidity standard of 0.5 McFarland. The prepared suspension from tested bacteria was transferred on solidified agar and spreaded uniformly. Synthetic antibacterial agents were dissolved in dimethyl sulfoxide (DMSO) to get stock with concentration of 1mg/ml [18,19]. After punching wells in agar using a sterile glass tube, 70µl of compounds and DMSO were transferred to each well. The zones around each well against defined bacteria after incubation for 24h, determinated the antibacterial power of each compound [20]. Ceftizoxime, Ciprofloxacin and DMSO were used with the same method as positive control and negative control respectively.
3.2 Broth dilution Method
In the next step for determination the lowest concentration of an antimicrobial agents that inhibits the visible growth of the tested microorganism (MIC value), broth dilution method was used [21]. In this study, eight sterile tubes were used for each compound and after transferring the broth culture medium into the tubes, dilution was done and 10µL of inoculum contained 1.5×106 C.F.U/ml of tested microorganism was added to each test tubes. After the incubation, the tubes were checked for the minimum inhibitory concentration concentration point. Ceftizixime, ciprofloxacin and DMSO respectively were also observed for comparative tests. Minimum Bactericidal Concentration (MBC) values were determined by subculturing of the tested tubes on agar media that show no visible bacterial growth [22].
3.3 Statistical analysis
We used Excel to do some basic data on three independent experiments,and the results are expressed as mean ± SEM.
4.1 Chemistry
We found that 3-fluorobenzoic acid derivatives 3a reacted with 2-pyridinecarbaldehyde 2 and N-isocyanoiminotriphenylphosphorane 1 in CH3CN react in a 1:1:1 ratio at room temperature to produce (5-(3-fluorophenyl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol 4a and, as a by-product, Ph3P=O 5 (Scheme 1). The reaction proceeded smoothly and cleanly under mild conditions in 74% yield, and no side reactions were observed. The other aromatic carboxylic acids also reacted smoothly to give similar products 4b-4f in yields of 71, 85% (Scheme1). We tried using the simple ketone analogous, 1-(2-pyridyl)-1-ethanone instead of 2-pyridinecarbaldehyde 2 in this reaction, but no corresponding products of type 4 were observed (Scheme1).
Scheme 1: Synthesis of (5-(fluoroaryl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol (4a-f)
The structures of the products were deduced from their IR, 1H and 13C NMR data. The 1H-NMR spectrum of 4a consisted of a singlet for CH aliphatic (δ= 6.24 ppm), a singlet for OH (δ= 6.63 ppm), exchangeable by D2O and multiple at δ= 7.31-8.93 ppm for the aromatic hydrogen atoms. The 1H decoupled 13C NMR spectrum of 4a showed eleven distinct resonances, partial assignment of these resonances is given in the experimental. The 1H and 13C NMR spectra of compounds 4b- 4f were similar to those of 4a, except for the aromatic moiety, which exhibited characteristic signals with appropriate chemical shifts.
A mechanistic rationalization for this reaction is depicted in Scheme 2. On the basis of the chemistry of isocyanides, it is reasonable to assume that the first step involves nucleophilic addition of 1 to 2-pyridinecarbaldehyde 2, facilitated by its protonation with the acid 3, leading to nitrilium intermediate 6. This intermediate may be attacked by the conjugate base of the acid 7 to form the 1:1:1 adduct 8. This adduct may undergo an intramolecular aza-Wittig reaction of the iminophosphorane moiety with the ester C=O group to afford the isolated (5-(fluoroaryl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol 4 by removal of Ph3P=O 5 from intermediate 9. In this reaction, the first two reaction steps are analogous to the well-known Passerini reaction, and the final step is analogous to the well-known intramolecularaza-Wittig reaction (tandem Passerini/intramolecularaza-Wittig sequence) (Scheme 2).
Scheme 2: Plausible mechanism for the (5-(fluoroaryl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol
4-2 Measurement of antimicrobial activity using Agar well diffusion Method
The antimicrobial activity of the synthesized derivatives was measured by zone of inhibition around each well. With comparison of zone of inhibition diameters of synthetic derivatives with Ceftizoxime and Ciprofloxacin drugs, the antibacterial power of oxadiazole derivatives were determined.
As shown in Figure 1 all the Oxadiazole derivatives that were synthesized in this research show significant anti actibacterial activity against Staphylococcus aureus with IZ of 16-21, whereas an IZ of 21-24mm was observed against Staphylococcus epidermidis and their antibacterial activity are notably more in compare with Ceftizoxime. No zone of inhibition was seen around the well containing DMSO (Negative control). (Figure1 and Table1).
Figure 1: Inhibition zone of compounds against Staphylococcus aureus and Staphylococcus epidermidis in 1mg/ml
NA:No ActivityThe result are expressed as mean ±sem*
Table1: Antibacterial activity of (5-(fluoroaryl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol derivatives by Agar well diffusion method (1mg/ml)
NA:No Activity The result are expressed as mean ±sem*
Table2: Antibacterial activity of (5-(fluoroaryl)-1,3,4-oxadiazol-2-yl) (pyridin-2-yl) methanol derivatives by broth dilution method(µg/mL)
The minimum inhibitory concentrations (MIC) of tested compounds (4a-f) are shown in (Table2). The MBC of compounds were three-fold higher than the corresponding MIC results. Compounds 4f were the most effective against S.aureus and S.epidermidis with MIC values of 15µg/mL and 31.25μg/mL respectively. while the MIC of the compounds 4f containing 4-trifluoromethylphenyl, were determined in the range of 31 to 62 µg/ml against S.aureus and S.epidermidis.
The investigation of antibacterial screening data revealed that all the tested compounds (4a-f) showed moderate to good inhibition at μg/ml in DMSO. This report intends to explore the role of electronic environment (fluorine atoms) on antibacterial activity. In our study, ring substitution by fluorine increased the antibacterial activity of the compounds in compared to compounds of our previous research [23]. The data found in the literature matching our research and claims that the compounds with halogen substituent are the most efficient against Gram-positive bacteria, particularly against S. aureus [24, 25]. In the course of this study, derivativs 4a-f possessing pyridine ring at the C-2 position on the linker of 1,3,4-oxadiazoles was identified as showing moderately enhanced antibacterial activity against gram positive bacteria as compared to our previous report so interesting activity of compounds 4a-f against Staphylococcus aureus and Staphylococcus epidermidis, which is much stronger than that seen against Gram negative bacteria can be correlated to this lipophilic group [26]. A limited effect is detected for the compound against Escherichia coli and Pseudomonas aeroginosa (MICs 500-1000 μg mL).
As in the presented results, the compounds had good antibacterial power, but in addition to the antimicrobial power of the synthesized derivatives, the presented one-step synthesis method can also be a very suitable method for the synthesis of derivatives with high antibacterial power and low financial and time cost.
This work was supported by Islamic Azad University, Urmia Branch.
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“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
