Anti-Infective Agents - Volume 20, Issue 4, 2022

Background: Emergence of drug resistance and severe side effects with current antitubercular drugs urges the development of more efficacious and safer new agents. The present study focused on this direction to develop new hetero-fused pyrimidines as potential antitubercular agents. Objective: The objective of the study was to synthesize and assess the antibacterial and antimycobacterial activity of novel 1,2,4-triazole ring bearing hetero-fused thienopyrimidines (6a-j & 7a-j). Also to evaluate the binding pattern of synthesized molecules at the target site and study their ADME properties by in silico tools. Methods: Two series of hetero fused thienopyrimidines (6a-j & 7a-j) were synthesized and tested for their antibacterial potentiality against B. subtilis, S. aureus, E. coli, and K. pneumonia. Compounds with potential antibacterial activity were further tested for their antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv and an isoniazid (INH)-resistant clinical sample of MTB using broth microdilution method. The binding efficacy at the enzyme site was evaluated by the molecular docking study using pantothenate synthetase (MTB-PS) (PDB: 3IVX) as the target protein. Further, in silico ADME properties of title compounds were explored by Swiss ADME online tools. Results: In this study, few compounds were found promising in exhibiting potent inhibitory activity against E. coli and MTB. Among these compounds, 6h (MTB: MIC-17.13±0.88 μM) and 6i (MTB: MIC-17.55±0.72 μM) displayed significant antimycobacterial activity. The molecular docking results suggested the efficient binding of biologically potential molecules. Conclusion: Compounds bearing N-benzyl moiety at the core nucleus with a p-nitro aryl side chain (6h) exhibited significant antitubercular activity. In silico studies showed effective binding at the target site and also indicated good compatibility in ADME properties.

Background: Developing new antibacterial and antiviral drugs are considered a significant issue due to the emergence and spread of resistant strains of microorganisms. The COVID-19 pandemic has dramatically increased the need for new broad-spectrum anti-infective agents. Objective: This experimental study aimed to investigate the antibacterial and phagocytic properties of silver-interferon preparation. The combination of properties of complex drugs makes them promising for treating drug-resistant infections and bacterial complications of viral diseases. Methods: The antibacterial effect of the silver-interferon platform was investigated by agar diffusion and serial dilution methods. The drug's effect on the functional activity of phagocytes was studied on human neutrophils in a Staphylococcus aureus uptake test. Results: Investigations have shown that the silver-interferon complex possesses a bactericidal mechanism of action against tested bacterial strains, including Streptococcus pneumonia, Salmonella enteritidis, Staphylococcus aureus, Escherichia coli. Streptococcus pneumonia was the most susceptible bacterial target for the tested complex, with a growth inhibition zone of 12±0.6 mm and a minimal bactericidal concentration of 0.08 mg/ml. A slight stimulating action of the drug in relation to the activity of phagocytes was revealed. Conclusion: Silver-interferon has proved as a prospective anti-infective drug with a wide range of activities.

Mucormycosis is the most emerging angioinvasive fungal infection of filamentous fungi of the Zygomycetes class, which, when neglected, causes severe disseminated infection along with significant chances of morbidity and mortality. The diagnosis and treatment remain challenging for the doctors. It has been observed that people who have been suffering from different diseases, such as hematological malignancies and uncontrolled diabetes, or who have gone through different surgeries, such as hematopoietic stem cell transplant, and solid transplantation, are the most affected ones. On the other hand, people who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) typically show the symptoms of mucormycosis after 1-2 weeks of successful recovery. Standard treatment of mucormycosis is traditionally considered an amphotericin B intravenous (IV) drug as initial therapy, although posaconazole and isavuconazole are also used. The core objective of the review is to typically focus on the area of the sudden cause of mucormycosis in the patients who have already recovered from SARS-CoV-2.

Background: Coronavirus disease 2019 (Covid-19) is caused by a novel coronavirus (SARS-CoV-2) infection, while influenza viruses cause the flu. SARS-CoV-2 and influenza virus co-infection seems to be a real and serious concern. Objective: This study aims to evaluate the clinical features, laboratory investigations, computed tomography scans, and interventions of Covid-19 patients during seasonal influenza. Methods: This was a multi-center prospective cohort study that collected data from hospitals, clinics, and laboratories on measurements, treatments, and outcomes from Covid-19 patients admitted to temporary Covid-19 care centers. Results: A total of 480 individuals (female, 231 [48.12%]; male, 249 [51.88%]) were recruited from March 31st to May 14th, 2021 at five hospitals/clinics in Uttar Pradesh, North India. The patients were divided into six groups based on their age (65+ years [25.41% of cases] being the most affected age) and five groups based on their conditions (asymptomatic 65 [13.54%], mild 94 [19.58%], moderate 206 [42.91%], severe 84 [17.50%] and critical 31 [6.45%]). Patients’ outcomes were documented as death (19 [3.95%]), recovery (421 [87.71%]) and undertreatment (40 [8.34%]). Conclusion: The most common clinical symptoms reported were fever, sore throat, and dyspnea. The severity was linked to hypoxemia, lymphocytopenia, thrombocytopenia, elevated erythrocyte sedimentation rate (ESR), and high blood urea nitrogen (BUN). The vast majority of patients were given symptomatic treatment. Any onset of fever should be suspected and examined for the viral strain to distinguish between Covid-19 and the seasonal flu.

Background: The chemical modification of pyridazinone leads to a potent therapeutic agent. Aims: A series of novel analogues of 4,5-dichloro-6-(substituted-benzyl)-2-(5-mercapto-[1,3,4]- oxadiazol-2-ylmethyl)-2H-pyridazin-3-one have been synthesized. Objectives: The novel synthesized pyridazinone derivatives were docked for possible targets, followed by antimicrobial and antioxidant activities. Methods: The target compounds were synthesized using a nucleophilic substitution reaction. The structures of newly synthesized compounds were confirmed by FT-IR, ¹H-NMR, ¹³C-NMR, mass spectroscopy, and elemental analysis. Results: The novel synthesised compounds were screened for their antimicrobial and antioxidant properties in vitro. Compound 5e showed good antibacterial and antifungal activity with MIC 25 μg/mL and 6.25 μg/mL against all the bacterial and fungal strains and in-vitro antioxidant activity with an IC50 of 51.64. The experimental results were further supported by molecular docking analysis using V-Life Science MDS 4.6 software and the GRIP batch docking method. Conclusion: All the compounds have been evaluated in vitro for antioxidant and antimicrobial activities against several strains of microbes and have shown significant activity. The experimental results were further supported by molecular docking analysis, describing improved interaction patterns.

Objective: This study aims to determine the in vitro antioxidant and antimicrobial properties of Nephrolepis biserrata (Sw.) Schott leaf extracts against different microbial strains, including 4 gram-positive bacteria, 4 gram-negative bacteria, 3 yeast, and 4 mould. Methods: The agar well diffusion method examined the antimicrobial activity of Nephrolepis biserrata leaf extracts against test micro-organisms. Additionally, TPC (total phenolic content), TFC (total flavonoid content), and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay of extracts were determined. Results: Preliminary phytochemical screening of all three extracts revealed the presence of tannins, terpenoids, alkaloids, saponin glycosides, and flavonoids. Results obtained were compared with the antibiotics Amphotericin B, Fluconazole, and Gentamicin used as standards. The mean zones of inhibition of methanol extract varied from 7 to 25 mm. However, with petroleum ether extract, the range varied from 9 to 12 mm and with acetone extract, the range was from 8 to 13 mm at two different concentrations of 250 and 500μg/disc. All extracts possessed significant antimicrobial activity against bacterial strains including Bacillus cereus, B. subtilis, Staphylococcus aureus, S. epidermis, Pseudomonas aeuginosa, Escherichia coli, Proteus Vulgaris, and Klebsiella pneumonia compared to fungal microbes such as Cryptococcus luteolus, Candida albicans, C. tropicalis, Aspergillus candidus, A. niger, and Mucor hiemalis wehmer, respectively. However, amongst all the three extracts, methanol leaf extract showed maximum antimicrobial activity. Conclusion: From the present study, it has been summarized that the antimicrobial activity of plants might be due to the presence of flavonoids and tannin components. In conclusion, still advanced research is required to isolate the active principles from plant extracts, showing antimicrobial activity that may lead to the development of a phytomedicine.

Background: SARS-CoV-2 infection has spread throughout the globe and has become a terrible epidemic. Researchers all around the globe are working to understand the characteristics of coronavirus and are trying to find antiviral compounds as an alternative to vaccines. Objective: The present study has been conceptualized to screen the various metabolites of traditional therapeutic plants that can have crucial antiviral activity against COVID-19. Methods: Medicinal plants are rich sources of therapeutic agents of human origin. In this study, active metabolites from plants such as O. sanctum, C. longa, A. indica, Z. officinale, A. paniculata, G. glabra, A. sativum, P. guajava, V. negundo and S. aromaticum have been studied. This study aims to control COVID-19, either by interfering with the Cysteine-like protease (3CLpro) component of COVID-19 or by blocking viral entry via the human angiotensinconverting enzyme 2 (ACE 2) receptor. The molecular docking of forty plant metabolites was studied with the 3Clpro component and ACE 2 receptors. In addition to this, the binding capacity of these two targets was also compared with hydroxychloroquine used for its treatment. Results: The results reveal that Glycyrrhizin binds to 3CLpro in a highly stable manner with the lowest binding energy. Glabridin, beta-sitosterol, beta-Caryophyllene, alpha-Curcumene, and Apigenin, among others, have shown effective interactions with both ACE 2 and 3CLpro. The study reveals the ability of more than 20 plant-based compounds against the COVID-19 infection cycle, which are more effective than hydroxychloroquine. Conclusion: Medicinal plant-based therapeutic compounds might provide quickly, sensitive, precise, and cost-effective alternative therapies. To reduce adverse effects, many pharmacological characteristics of medicinal plant agents should be adjusted.

Background: Mentha piperta L. var peppermint oil is one of the most important essential oil products in the world due to its application in the pharmaceutical, food, and cosmetic industries. Objective: The present study aimed to examine the biological activities, including antioxidant and antimicrobial potentials of oil extracted from peppermint leaves using a solvent extraction method. Methods: The oil extraction was done in the Soxhlet apparatus using hexane as a solvent. The antimicrobial experiment was conducted as three factor experiment involving one source extract, hexane as a solvent, and four test pathogens completely randomized in three replications. Results: The results of physicochemical properties of peppermint oil indicated that oil yield (41.15%), specific gravity (0.90), acid value (1.54mg/g), free fatty acid (0.78%), and peroxide value (3.70). The antioxidant activities were assessed based on ascorbic acid content, DPPH, and hydrogen peroxide free radical scavenging activities. The M. piperita leaf oil was recorded with ascorbic acid content (45.56%), 2,2-diphenyl-1-picrylhydrazyl DPPH (9.50%) and hydrogen peroxide free radical scavenging activity (78.30%). The mean zone of inhibition against bacterial pathogens ranged from 11.80±0.42 mm to 16.75±0.35mm, while 14.65±0.50to 16.75±0.28mm against fungal pathogens. The oil extract exhibited the strongest bactericidal activity with MIC (0.03μl/ml) and the corresponding MBC (0.06 μl/ml) against S. aureus for antifungal activity. C albicans was the most susceptible to MIC (0.12μl/ml) and MFC (0.25μl/ml). Conclusion: The result of this study was that the physicochemical properties and antioxidant activities of peppermint oil extract demonstrated the quality and stability of the oil extract.

Introduction: The purpose of this study was to evaluate the antimalarial, antibacterial, antifungal, antioxidant, and anti-inflammatory properties of Emblica officinalis fruit ethanol extract. Methods: Emblica officinalis fruit extract was prepared using the Soxhlet apparatus at room temperature for 48 hours with 99% ethanol and 1% of double-distilled water. GCMS was used to determine the phytoconstituent profile of an extract of Emblica officinalis fruit, and in-vitro assays were used to assess the biological activities. Results: Malic acid, pyrogallol, cinnamic acid, pidolic acid, L-glucose, palmitic acid, linoleic acid, gallic acid, ellagic acid, heneicosane, and levoglucosenone were identified in the extract by GCMS analysis. The ethanol extract of Emblica officinalis fruit showed antimalarial activity against Plasmodium falciparum with EC50=13.68 g/ml and antibacterial activity with MIC=6.25μg/ml and MIC=12.5 μg/ml against Staphylococcus aureus and Salmonella typhi, respectively. Also, significant antifungal activity of the extract was observed with MIC=6.25μg/ml on Aspergillus niger. Conclusion: The extract showed excellent affinity to scavenge the free radicals and protection of protein denaturation, which indicates its antioxidant and anti-inflammatory effects, respectively. These protective effects may possibly be due to therapeutically active compounds present in Emblica officinalis fruit.

Introduction: The study of novel Schiff bases and their metal complexes has achieved enormous attention of inorganic as well as medicinal chemists. Objective: The objective of this study is to study the structural elucidation and antimicrobial screening of 3-formylchromone and 3-aminoquinoline-based Schiff base and their metal complexes. Methods: Cu(II) and Co(II) complexes of 3-((quinolino-3-ylimino) methyl)-4H-chromen-4- one ligand were synthesized and characterized by elemental analysis, molar conductivity measurement, infrared, UV-Visible, ¹H NMR spectral studies, thermogravimetric analysis, and powder X-ray diffraction studies. Results: Antibacterial activity of synthesized compounds were screened against Klebsiella pneumoniae, Staphylococcus aureus, and Proteus vulgaris, and antifungal activity was screened against fungi Candida albicans and Aspergillus niger. Schiff base ligand and their Cu(II) and Co(II) complexes revealed significant antibacterial and antifungal activity against tested strains. Octahedral geometry of metal complexes was proven by analytical, physical, and spectral data. Conclusion: In this present work, novel Schiff base 3-((quinolino-3-ylimino) methyl)-4Hchromen- 4-one and its Cu(II) and Co(II) complexes revealed promising antibacterial and antifungal activities.