Recent Advances in Anti-Infective Drug Discovery Formerly Recent Patents on Anti-Infective Drug Discovery - Volume 17, Issue 1, 2022

Background: COVID-19 is still soaring, and the new delta COVID-19 variant is on the rise and spreading around the world. Objective: We conducted a patent analysis to better understand the therapeutic strategy developed for antivirals available for the disorders of the respiratory system. Materials and Methods: European granted patents filed from January 2002 to June 2021 were analyzed. We used a combination of International patent classification (IPC) “A61p31/12” and “A61p11/00” to search the relevant documents. Results: Our study showed R of antiviral drugs for disorders of the respiratory system to be decreasing over the past 20 years. Chemical drugs showed various chemical structures. The development of chemical drugs or herbal medicines appeared to commence earlier than the biological products. Also, the results indicated that large global companies play a leading role in developing kinase inhibitors as chemical drugs. Conclusion: There are three strategies for developing antiviral drugs for the disorders of the respiratory system, including chemical drugs, herbal medicines or natural products, and biological products. Herbal medicines may provide a new insight and approach to developing antiviral drugs for disorders of the respiratory system. A combination of chemical drugs and natural products may be a promising therapeutic method for treating patients with COVID- 19.

Background: Plant-derived products have been used in medicine as a source of bioactive molecules, mainly due to their medicinal importance and therapeutic potential. Nowadays, plant derived products have been used in the medicine for the development of novel drug leads. Polyphenols are an important class of secondary metabolites found to be present in plants and their derived products. Polyphenols play an important role in the nutrition of human beings and also have a significant role in plant resistance against pests and diseases. Scientific studies have proven the biological importance of flavonoids in medicine and other allied health sectors. Anti-oxidant, analgesic, anti-microbial, anti-inflammatory, anti-viral, anti-tumor and anti-allergic activities are the important pharmacological features of flavonoids. Irisolidone is an important isoflavone found to be present in Pueraria lobata flowers. Methods: To know the medicinal importance and therapeutic potential of irisolidone in the medicine, numerous scientific research data have been collected from Google, Google Scholar, PubMed, Science Direct, and Scopus. Pharmacological activity data of irisolidone has been collected and analyzed in the present works to know their health beneficial aspects in the medicine. Detailed pharmacological activities of irisolidone have been investigated through scientific data analysis of scientific research works. Results: Scientific research data analysis of irisolidone revealed the anti-inflammatory, antiangiogenic, anti-cancer, anti-platelet, anti-oxidant, anti-hyperlipidemic, immunomodulating, hepatoprotective and estrogenic potential. However, the biological effect of irisolidone on the gastric system, aldose reductase enzymes, malignant gliomas, and JC virus has also been investigated. Scientific data analysis revealed the significance of analytical tools for the separation and identification of irisolidone. Conclusion: Present work signified the biological importance and therapeutic potential of irisolidone in medicine.

Background: Several in vitro and in vivo biological activities of serotonin, 5- hydroxytryptamine (5-HT), as a bioactive molecule, and its transporter (5-HT-Tr) were evaluated in parasitic infections. Objective: Herein, the roles of 5-HT and 5-HTR in helminths and protozoan infections with medical and veterinary importance are reviewed. Methods: We searched information in 4 main databases and reviewed published literature about the serotonin transporter's role as a promising therapeutic target against pathogenic parasitic infections between 2000 and 2021. Results: Based on recent investigations, 5-HT and 5-HT-Tr play various roles in parasite infections, including biological function, metabolic activity, organism motility, parasite survival, and immune response modulation. Moreover, some of the 5-HT-TR in Schistosoma mansoni showed an excess of favorite substrates for biogenic amine 5-HT compared to their mammalian hosts. Furthermore, the main neuronal protein related to the G protein-coupled receptor (GPCR) was identified in S. mansoni and Echinococcus granulosus, playing main roles in these parasites. In addition, 5-HT increased in toxoplasmosis, giardiasis, and Chagas disease. On the other hand, in Plasmodium spp., different forms of targeted 5-HTR stimulate Ca²⁺ release, intracellular inositol triphosphate (ITP), cAMP, and protein kinase A (PKA) activity. Conclusion: This review summarized the several functional roles of the 5-HT and the importance of the 5-HT-TR as a drug target with minimal harm to the host to fight against helminths and protozoan infections. Hopefully, this review will shed light on research regarding serotonin transporter-based therapies as a potential drug target soon.

Background: The increase in bacterial resistance against antibiotics is thought to be another type of pandemic after COVID-19. Emergency treatment based on antibiotics is a major influence in increasing this resistance. Bacteria, such as Klebsiella pneumoniae, are the most affected by the indiscriminate use of antibiotics, since they are resistant to most antibiotics currently available on the market. Objective: This review aimed to evaluate patents of new drugs and formulations, for the treatment of infections caused by Klebsiella pneumoniae. Methods: The present patent review was carried out through a specialized search database Espacenet. The selection was based on the criteria of patents published from 2010 to May 2021, in any language, and containing the keywords in title or abstract. Also, a research was performed on the PubMed database, using the inclusion criteria. Results: Twenty-two patents were selected for the analysis according to the aim of the study. The advance of new patents has been mostly observed in the World Intellectual Property Organization, China, and United States. The results showed that the main approach was the drug association, followed by drug carriers, new isolated products, and vaccines. Conclusion: It has been observed that few studies use new drug alternatives for the treatment, probably due to the higher cost of the development and lack of investments. The effectiveness and safety of these therapies depend on the acceptance, the correct prescription, and rational use of medicines. Therefore, this review can further develop new treatments as alternatives against Klebsiella pneumoniae and pneumonia caused by it.

Background: The design of hybrid compounds is a distinct approach for developing potent bioactive agents. Carvacrol, an essential oil, exhibits antimicrobial, antifungal, antioxidant, and anticancer activity, making it a good precursor for the development of compounds with potent biological activities. Some patents have reported carvacrol derivatives with promising biological activities. Objective: This study aimed to prepare hybrid compounds containing a carvacrol scaffold with significant antibacterial and anticancer activity. Methods: Esterification reactions between carvacrol and known pharmacophores were performed at room temperature and characterized using ¹H-NMR, ¹³CNMR, and UHPLC-HRMS. In vitro antibacterial study was determined using the microdilution assay and cytotoxicity evaluation using sulforhodamine B staining assay. Results: The FTIR spectra of the carvacrol hybrids revealed prominent bands in the range of 1612-1764 cm^-1 and 1014-1280 cm^-1 due to (C=O) and (C-O) stretching vibrations, respectively. The structures of the carvacrol hybrids were confirmed by ¹H-NMR, ¹³C-NMR, and UHPLC-HRMS analysis, and compound 5 exhibited superior activity when compared to the hybrid compounds against the strains of bacteria used in the study. The in vitro cytotoxicity evaluation showed that compound 3 induced cytotoxicity in all the cancer cell lines; MDA (16.57 ± 1.14 μM), MCF-7 (0.47 ± 1.14 μM), and DU145 (16.25 ± 1.08 μM), as well as the normal breast cells, MCF-12A (0.75± 1.30 μM). Compound 7 did not induce cytotoxicity in the cell lines tested (IC50 > 200 μM). Conclusion: The modification of carvacrol through hybridization is a promising approach to develop compounds with significant antibacterial and anticancer activity.

Background: Mycobacterium tuberculosis (Mtb) is an organism that causes tuberculosis (TB). In 2019, 10 million individuals worldwide contracted tuberculosis, with 1.4 million people dying from the disease each year (World Health Organization, 2021). Hydrazones- hydrazide-based drugs have been shown to be bactericidal against M. tuberculosis replication. Objectives: We herein intended to synthesize a series of acid hydrazones (3a-3l) by condensing 4-nitrobenzohydrazine with substituted aromatic acids in ethanol at room temperature. Materials and Methods: All newly synthesized compounds were characterized by standard spectroscopic techniques. Synthesized compounds were then tested for anti-mycobacterial activity against H37Rv strains. Molecular docking analysis was performed for three crystal structures of 1ENY, 1TED and 2FUM Mycobacterium tuberculosis receptors. Results: Among all tested molecules, 3i (MIC: 50 μg/mL) and 3b (MIC: 50 μg/mL) were found to be the best ligands for further development of new anti-TB drug. We found that our proposed molecules have higher docking scores, corresponding standard anti-TB agents, such as ciprofloxacin and isoniazid. Synthesized compounds were found to have druglikeness properties when tested with Lipinski’s filter for drug-likeness. Conclusion: Our current study proposes N'-arylidene-4-nitrobenzohydrazides as anti-TB agents. Agents with such system can be developed in future for development into active lead molecules.