Current medicinal chemistry
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Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but the outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. ⋯ Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body's immune system to fight cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.
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The immune system actively counteracts the tumorigenesis process; a breakout of the immune system function, or its ability to recognize transformed cells, can favor cancer development. Cancer becomes able to escape from immune system control by using multiple mechanisms, which are only in part known at a cellular and molecular level. Among these mechanisms, in the last decade, the role played by the so-called "inhibitory immune checkpoints" is emerging as pivotal in preventing the tumor attack by the immune system. ⋯ An outline of the immune checkpoint targeting approaches, also including combined immunotherapies and the existing trials, is also provided. Notwithstanding the great efforts devoted by researchers in the field of biomarkers of response, to date, no validated FDA-approved immunological biomarkers exist for cancer patients. We highlight relevant studies on predictive biomarkers and attempt to discuss the challenges in this field, due to the complex and largely unknown dynamic mechanisms that drive the tumor immune tolerance.
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Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease-19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir [which is widely used to treat Human Immunodeficiency Virus (HIV) infection] in combination with the anti-flu drug oseltamivir. ⋯ Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.
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Studies on fluorinated inhalation anesthetics, including synthesis, physical chemistry and pharmacology, have been summarized in this review. Retrospecting the history of inhalation anesthetics revealed their increasing reliance on fluorine and ether structures. Halothane causes a rare but severe immune-based hepatotoxicity, which was replaced by enflurane in the 1970s. ⋯ Moreover, the anesthetic activity cannot be simply predicted from the molecular structures but has to be inferred from the experiments. Several regularities were found by experimental studies: 1) the potency and toxicity of the saturated linear chain halogenated ether are enhanced when its molecular weight is increased; 2) the margin of safety decreases and the recovery time is prolonged when the boiling point of the candidate increases; and 3) compounds with an asymmetric carbon terminal exhibit good anesthesia. Nevertheless, the development of new inhalation anesthetics, better than desflurane and sevoflurane, is still challenging not only because of the poor structure/activity relationship known so far but also due to synthetic issues.
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In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and then spread worldwide. Due to a lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find a therapeutic solution. ⋯ Scientists all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.