Recent Advances in Anti-Infective Drug Discovery Formerly Recent Patents on Anti-Infective Drug Discovery - Volume 19, Issue 4, 2024

Background: Plant products derived from natural sources have been used in medicine as a raw material and newer kinds of drug molecules in pharmaceuticals and other allied health sectors. Phytochemicals have numerous medicinal potentials, including anti- ageing, anti-carcinogenic, anti-microbial, anti-oxidant, and anti-inflammatory activity in medicine. Development and biological application of herbal products in modern medicine signified the value of traditional medicinal plants in health care systems. Methods: The objective of the present study was to explore the scientific knowledge of the medicinal importance and therapeutic potential of artemetin in medicine. However, scientific investigations for their pharmacological activities in medicine have been done through scientific data analysis of different scientific research work collected from PubMed, Google, Science Direct and Google Scholar in order to know the biological importance of artemetin in medicine. Moreover, analytical data of artemetin have also been discussed in the present work. Results: The present work scientific data signified the biological potential of artemetin in medicine. Artemetin has been derived from numerous medicinal plants and dietary herbs, including Artemisia absinthium, Artemisia argyi, Achillea millefolium, and Vitex trifolia. Artemetin has anti-malarial, anti-oxidant, anti-apoptotic, anti-microbial, anti-tumoral, antiatherosclerotic, anti-inflammatory, hypotensive and hepatoprotective effects. Further, the biological role of artemetin on lipid oxidation, cytokine production, lipoxygenase, and estrogen- like effects was also investigated in the present work. Analytical data on artemetin in the present paper signified their important role in the isolation, separation, and identification of different classes of pure phytochemicals, including artemetin in medicine. Conclusion: Scientific data analysis of artemetin signified its therapeutic potential in medicine for the development of newer scientific approaches for different human disorders.

Background: Ebola virus (EBOV) is a genus of negative-strand RNA viruses belonging to the family Filoviradae that was first described in 1976 in the present-day Democratic Republic of the Congo. It has intermittently affected substantial human populations in West Africa and presents itself as a global health menace due to the high mortality rate of patients, high transmission rate, difficult patient management, and the emergence of complicated autoimmune disease-like conditions post-infection. Objective: EBOV or other EBOV-like species as a biochemical weapon pose a significant risk; hence, the need to develop both prophylactic and therapeutic medications to combat the virus is unquestionable. Methods: In this review work, we have compiled the literature pertaining to transmission, pathogenesis, immune response, and diagnosis of EBOV infection. We included detailed structural details of EBOV along with all the available therapeutics against EBOV disease. We have also highlighted current developments and recent advances in therapeutic approaches against Ebola virus disease (EVD). Discussion: The development of preventive vaccines against the virus is proving to be a successful effort as of now; however, problems concerning logistics, product stability, multi- dosing, and patient tracking are prominent in West Africa. Monoclonal antibodies that target EBOV proteins have also been developed and approved in the clinic; however, no small drug molecules that target these viral proteins have cleared clinical trials. An understanding of clinically approved vaccines and their shortcomings also serves an important purpose for researchers in vaccine design in choosing the right vector, antigen, and particular physicochemical properties that are critical for the vaccine’s success against the virus across the world. Conclusion: Our work brings together a comprehensive review of all available prophylactic and therapeutic medications developed and under development against the EBOV, which will serve as a guide for researchers in pursuing the most promising drug discovery strategies against the EBOV and also explore novel mechanisms of fighting against EBOV infection.

Background: Endometriosis is one of the common diseases of women, especially in reproductive age, and it is one of the most important causes of infertility in women. The aim of this study was to investigate the level of mRNA-TLR-5 expression in women with endometriosis. Methods: The present study was performed in Nikan Hospital, Tehran, Iran, in 2021. The samples of endometrial mucosa for the eutopic group and an ovarian endometriotic cyst for the ectopic group were obtained from the patients who underwent laparoscopic surgery at the Fetal Infertility Center and were diagnosed with endometriosis. Normal endometrial samples were also obtained from patients who had no history of infertility and underwent laparoscopic TL surgery for reasons other than endometriosis such as ovarian cysts (control group). After RNA extraction and cDNA synthesis, TLR-5 gene expression was evaluated by the Real-Time PCR method. Results: Based on the results of the comparison of TLR-5 gene expression in all three ectopic, eutopic endometrium, and control groups by Real-Time PCR, it was found that the TLR-5 gene expression is significantly higher in ectopic samples than in the other two groups, but there is a significant difference between two utopic and control groups. Conclusion: The increase in TLR-5 expression in the ectopic group can probably be a reason for reducing the apoptosis of cells entered into the peritoneal cavity and creating an environment for the survival and proliferation of these cells.

Background: Acinetobacter baumannii is an opportunistic hospital pathogen with high antibiotic resistance, and the ability to produce biofilm. This study aimed to investigate epsA, ompA, and bap genes involved in biofilm formation in MDR and XDR clinical isolates of Acinetobacter baumannii in Khorramabad, Iran. Methods: In this study, 79 A. baumannii isolates were collected from various samples of the patients admitted to tertiary hospitals in Khorramabad city, Iran, between January and August 2019. After performing the semi-quantitative evaluation of biofilm production by microtiter plate assay, screening of isolates carrying epsA, ompA, and bap genes was done by PCR method. Finally, statistical analyses were conducted using SPSS 22. Results: Among 79 A. baumannii isolates, 52% XDR, 40% MDR, and 16% non-XDRMDR isolates were found to be biofilm producers. All XDR and 94% MDR isolates had ompA and epsA genes, and bap genes were detected among > 80% of these isolates. Moreover, the presence of biofilm-related genes and biofilm production among non-XDRMDR isolates were less than among resistant isolates (p≤ 0.01). Conclusion: Based on the results, biofilm production and simultaneous presence of epsA, ompA, and bap genes among MDR, and XDR A. baumannii isolates have been found to be significantly more than non-XDR-MDR isolates.

Background: The pleiotropic effect of cholecalciferol (vitamin D3) has gained significant momentum and has been explored widely. Objectives: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli. Methods: An in vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method. Results: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli. Conclusion: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents.

Background: Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved for the treatment of uncomplicated and complicated skin and soft tissue infections caused by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most cases. However, prolonged therapy is associated with various side effects and lifethreatening complications. Cutaneous application of LNZ will assist in reducing the dose, hence minimizing the unwanted side/adverse effects associated with oral administration. Dermal delivery provides an alternative route of administration, facilitating a local and sustained concentration of the antimicrobial at the site of infection. Objective: The current research work aimed to formulate solid lipid nanoparticles (SLNs) based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft tissue infections to maximise its benefits and minimise the side effects. Methods: SLNs were prepared by high-shear homogenisation and ultrasound method using Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration, drug-to-lipid ratio, and sonication time was investigated on particle size, zeta potential, and entrapment efficiency using the Taguchi design. The main effect plot of means and signal-to-noise ratio were generated to determine the optimized formulation. The optimized batch was formulated into a gel, and ex vivo permeation study, in vitro and in vivo antibacterial activity were conducted. Results: The optimised process parameters to achieve results were 2% surfactant concentration, a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was 206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in vitro drug release. The gel showed a 5.03 ± 0.15 cm zone of inhibition while evaluated for in vitro antibacterial activity against Staphylococcus aureus. Ex vivo skin permeation studies demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results showed a significant reduction in colony-forming units in the group treated with LNZ SLN-based gel. Conclusion: Ex vivo studies ascertain the presence of the drug at the desired site and improve therapy. In vivo results demonstrated the ability of SLN-based gel to significantly reduce the number of bacteria in the stripped infection model. The utilization of SLN as an LNZ carrier holds significant promise in dermal delivery.