Current Drug Targets - Volume 23, Issue 2, 2022

Fungal infections have shown an upsurge in recent decades, which is mainly because of the increasing number of immunocompromised patients and the occurrence of invasive candidiasis has been found to be 7-15 fold greater than that of invasive aspergillosis. The genus Candida comprises more than 150 distinct species, however, only a few of them are found to be pathogenic to humans. Mortality rates of Candida species are found to be around 45% and the reasons for this intensified mortality are inefficient diagnostic techniques and unfitting initial treatment strategies. There are only a few antifungal drug classes that are employed for the remedy of invasive fungal infections. which include azoles, polyenes, echinocandins, and pyrimidine analogs. During the last 2-3 decades, the usage of antifungal drugs has increased several folds due to which the reports of escalating antifungal drug resistance have also been recorded. The resistance is mostly to the triazole- based compounds. Due to the occurrence of antifungal drug resistance, the success rates of treatment have been reduced as well as major changes have been observed in the frequency of fungal infections. In this review, we have summarized the major molecular mechanisms for the development of antifungal drug resistance.

The emergence of multi-drug resistant bacteria and limitations on cancer treatment represent two important challenges in modern medicine. Biological compounds have been explored with a particular focus on venoms. Although they can be lethal or cause considerable damage to humans, venom is also a source rich in components with high therapeutic potential. Viperidae family is one of the most emblematic venomous snake families and several studies highlighted the antibacterial and antitumor potential of viper toxins. According to the literature, these activities are mainly associated to five protein families - svLAAO, Disintegrins, PLA2, SVMPs and C-type lectins- that act through different mechanisms leading to the inhibition of the growth of bacteria, as well as, cytotoxic effects and inhibition of metastasis process. In this review, we provide an overview of the venom toxins produced by species belonging to the Viperidae family, exploring their roles during the envenoming and their pharmacological properties, in order to demonstrate its antibacterial and antitumor potential.

Endometrial cancer is one of the three most common malignant tumors in the female reproductive system. Advanced and recurrent endometrial cancers have poor prognoses and lack effective treatments. Poly (ADP-ribose) polymerase (PARP) inhibitors have been applied to many different types of tumors, and they can selectively kill tumor cells that are defective in homologous recombination repair. Endometrial cancer is characterized by mutations in homologous recombination repair genes; accordingly, PARP inhibitors have achieved positive results in off-label treatments of endometrial cancer cases. Clinical trials of PARP inhibitors as monotherapies and within combination therapies for endometrial cancer are ongoing. For this review, we searched PubMed with “endometrial cancer” and “PARP inhibitor” as keywords, and we used “olaparib”, “rucaparib”, “niraparib” and “talazoparib” as search terms in clinicaltrials.gov for ongoing trials. The literature search ended in October 2020, and only English-language publications were selected. Multiple studies confirm that PARP inhibitors play an important role in killing tumor cells with defects in homologous recombination repair. Its combination with immune checkpoint inhibitors, PI3K/AKT/mTOR pathway inhibitors, cell cycle checkpoint inhibitors, and other drugs can improve the treatment of endometrial cancer.

The gut has been colonized with bacteria, fungi, viruses, archaea, eukarya. The human and bacterial cells are found in a 1:1 ratio, while the variance in the diversity of gut microbiota may result in dysbiosis. Gut dysbiosis may result in various pathological manifestations. Beneficial gut microbiota may synthesize short-chain fatty acids like acetate, butyrate, propionate. Gram-negative organisms are the primary source of LPS, a potent pro-inflammatory mediator. Both gut microbiota and microbial products may be involved in immunomodulation as well as inflammation. Prebiotics and probiotics are being explored as therapeutic agents against various inflammatory and autoimmune disorders. Here, we discuss the molecular mechanisms involved in gut bacteria mediated modulation of various inflammatory and autoimmune disorders.

Spreading rapidly in recent years, cancer has become one of the causes of the highest mortality rates after cardiovascular diseases. The reason for cancer development is still not clearly understood despite enormous research activities in this area. Scientists are now working on the biology of cancer, especially on the root cause of cancer development. The aim is to treat the cancer disease and thus cure the patients. The continuing efforts for the development of novel molecules as potential anti-cancer agents are essential for this purpose. The main aim of this review was to present a survey on the medicinal chemistry of thioethers and provide practical data on their cytotoxicities against various cancer cell lines. The research articles published between 2001-2020 were consulted to prepare this review article; however, patent literature has not been included. The thioether-containing heterocyclic compounds may emerge as a new class of potent and effective anti-cancer agents in the future.

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