Mini Reviews in Medicinal Chemistry - Volume 22, Issue 16, 2022

Tuberculosis (TB), a highly fatal infectious disease, is caused by Mycobacterium tuberculosis (Mtb) that has inflicted mankind for several centuries. In 2019, the staggering number of new cases reached 10 million resulting in 1.2 million deaths. The emergence of multidrug-resistance- Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant-Mycobacterium tuberculosis (XDR-TB) is a global concern that requires the search for novel, effective, and safer short-term therapies. Nowadays, among the few alternatives available to treat resistant-Mtb strains, the majority have limitations, which include drug-drug interactions, long-term treatment, and chronic induced toxicities. Therefore, it is mandatory to develop new anti-Mtb agents to achieve health policy goals to mitigate the disease by 2035. Among the several bioactive anti-Mtb compounds, chalcones have been described as the privileged scaffold useful for drug design. Overall, this review explores and analyzes 37 chalcones that exhibited anti-Mtb activity described in the literature up to April 2021 with minimum inhibitory concentration (MIC90) values inferior to 20 μM and selective index superior to 10. In addition, the correlation of some properties for most active compounds was evaluated, and the main targets for these compounds were discussed.

Polymers have an endless scope due to their flexibility, amendment, and modification with the organic and inorganic compounds. There is an intense competition between natural and synthetic biodegradable polymers concerning biodegradability and compatibility with modern technology. Biodegradable polymers play a significant role in sustaining humanity on the earth due to nonenvironmental hazards. These polymers play a crucial role in biomedicine technology, such as tissue engineering, preparation of different scaffolds, drug delivery systems, industrial sector, agriculture, and food packaging. Here, we probed on various applications, challenges, and the limitations of biodegradable polymers in life.

The SARS-CoV-2 enters the human airways and comes into contact with the mucous membranes lining the mouth, nose, and eyes. The virus enters the healthy cells and uses cell machinery to make several copies itself. Critically ill patients infected with SARS-CoV-2 may have damaged lungs, air sacs, lining, and walls. Since COVID-19 causes cytokine storm, it damages the alveolar cells of the lungs and fills them with fluid, making it harder to exchange oxygen and carbon dioxide. The SARS-CoV-2 infection causes a range of complications, including mild to critical breathing difficulties. It has been observed that older people suffering from health conditions like cardiomyopathies, nephropathies, metabolic syndrome, and diabetes instigate severe symptoms. Many people who died due to COVID-19 had impaired metabolic health [IMH], characterized by hypertension, dyslipidemia, and hyperglycemia, i.e., diabetes, cardiovascular system, and renal diseases, making their retrieval challenging. Jeopardy stresses for increased mortality from COVID-19 include older age, COPD, ischemic heart disease, diabetes mellitus, and immunosuppression. However, no targeted therapies are available as of now. Almost two-thirds of diagnosed coronavirus patients had cardiovascular diseases and diabetes, out of which 37% were under 60. The NHS audit revealed that with a higher expression of ACE-2 receptors, viral particles could easily bind their protein spikes and get inside the cells, finally causing COVID-19 infection. Hence, people with IMH are more prone to COVID-19 and, ultimately, comorbidities. This review provides enormous information about tissue [lungs, heart, and kidneys] damage, pathophysiological changes, and impaired metabolic health of SARS-CoV-2 infected patients. Moreover, it also designates the possible therapeutic targets of COVID-19 and drugs which can be used against these targets.

Osthole, a naturally occurring coumarin-type compound, is isolated from the Chinese herbal medicine Cnidium monnieri (L.) and exhibits a broad range of biological properties. In this review, the total synthesis and structural modifications of osthole and its analogs are described. Additionally, the progress on bioactivities of osthole and its analogs has been outlined since 2016. Moreover, the structure-activity relationships and mechanisms of action of osthole and its derivatives are discussed. These can provide references for future design, development, and application of osthole and its analogs as drugs or pesticides in the fields of medicine and agriculture.

Background: More and more shreds of evidence show that the occurrence and development of tumors are closely related to the abnormal expression of LncRNA. A large number of experiments have found that overexpression or under-expression of MCM3AP-AS1 can affect the occurrence and development of cancer cells in varying degrees, such as proliferation, invasion, and translocation. Besides, MCM3AP-AS1 may become a promising target for many tumor biotherapies. This article reviews the pathophysiological functions and molecular mechanisms of MCM3AP-AS1 in various tumors. Methods: This paper systematically summarizes the published literatures in PubMed. The molecular mechanism of MCM3AP-AS1 in a variety of tumors is reviewed. Results: The abnormal expression of MCM3AP-AS1 in different tumors is closely related to tumor proliferation, invasion, and migration. MCM3AP-AS1 mediates or participates in related signaling pathways to regulate the expression of targeted miRNAs and proteins. MCM3AP-AS1 plays a vital role in tumor diagnosis and treatment. Conclusion: LncRNA MCM3AP-AS1 is a feasible tumor marker and a potential therapeutic target for many kinds of tumors.

Phosphatidyl-inositol-3-kinase (PI3K) has emerged as a potential therapeutic target for the development of novel anticancer drugs. The dysregulation of PI3K has been associated with many human malignancies such as breast, colon, endometrial, brain, and prostate cancers. The PI3K kinases in their different isoforms, namely α, β, δ, and γ, encode PIK3CA, PIK3CB, PIK3CD, and PIK3CG genes. Specific gene mutation or overexpression of the protein is responsible for the therapeutic failure of current therapeutics. Recently, various PI3K signaling pathway inhibitors have been identified, which showed promising therapeutic results by acting on specific isoforms of the kinase too. Several inhibitors containing medicinally privileged scaffolds like oxadiazole, pyrrolotriazine, quinazoline, quinazolinone, quinazoline-chalcone hybrids, quinazoline-sulfonamide, pyrazolochalcone, quinolone hydroxamic acid, benzofuropyridinone, imidazopyridine, benzoxazines, dibenzoxanthene, indoloderivatives, benzimidazole, and benzothiazine derivatives have been developed to target the PI3K pathway and/or a specific isoform. The PI3K inhibitors under clinical trial studies include GDC-0032, INK1117 for PI3K-α, and AZD8186 for PI3K-β. This review primarily focuses on the structural insights, anticancer activities, and structure-activity relationship (SARs) studies of recent PI3K inhibitors, including their clinical stages of development and therapeutic values.

This review seeks to clarify the factors involved in the various immune responses to SARSCoV- 2 infection and the mechanisms that influence the development of COVID-19 with severe evolution. The innate immune response that evolves against SARS-CoV-2 in a complex way is highlighted, integrating multiple pathways by coronaviruses to evade it, in addition to characterizing the adaptive immune response, which can lead to an effective immune response or can contribute to immunopathological imbalance. In turn, host-dependent biomarkers, such as age, gender, ABO blood group, and risk factors, that contribute to the critical and varied progress of COVID-19 immunopathogenesis are analyzed. Finally, the potential vaccine candidates are presented, capable of generating immune protection with humoral and/or cellular neutralizing responses, in favor of blocking and destroying both the new human coronavirus and its variants, which cause the current pandemic.