Mucormycosis: A hidden mystery of fungal infection, possible diagnosis, treatment and development of new therapeutic agents.

Mucormycosis is a fungal infection which got worsens with time if not diagnosed and treated. The current COVID-19 pandemic has association with fungal infection specifically with mucormycosis. Already immunocompromised patients are easy target for COVID-19 and mucormycosis as well. COVID-19 infection imparts in weak immune system so chances of infection is comparatively high in COVID-19 patients. Furthermore, diabetes, corticosteroid medicines, and a weakened immune system are the most prevalent risk factors for this infection as we discussed in case studies here. The steroid therapy for COVID-19 patients sometimes have negative impact on the patient health and this state encounters many infections including mucormycosis. There are treatments available but less promising and less effective. So, researchers are focusing on the promising agents against mucormycosis. It is reported that early treatment with liposomal amphotericin B (AmB), manogepix, echinocandins isavuconazole, posacanazole and other promising therapeutic agents have overcome the burden of mucormycosis. Lipid formulations of AmB have become the standard treatment for mucormycosis due to their greater safety and efficacy. In this review article, we have discussed case studies with the infection of mucormycosis in COVID-19 patients. Furthermore, we focused on anti-mucormycosis agents with mechanism of action of various therapeutics, including coverage of new antifungal agents being investigated as part of the urgent global response to control and combat this lethal infection, especially those with established risk factors.

Recent advances in the targeting of human DNA ligase I as a potential new strategy for cancer treatment.

The emergence of drug resistance, coupled with the issue of low tumor selectivity and toxicity is a major pitfall in cancer chemotherapy. It has necessitated the urgent need for the discovery of less toxic and more potent new anti-cancer pharmaceuticals, which target the interactive mechanisms involved in division and metastasis of cancer cells. Human DNA ligase I (hligI) plays an important role in DNA replication by linking Okazaki fragments on the lagging strand of DNA, and also participates in DNA damage repair processes. Dysregulation of the functioning of such ligases can severely impact DNA replication and repair pathways events that are generally targeted in cancer treatment. Although, several human DNA ligase inhibitors have been reported in the literature but unfortunately not a single inhibitor is currently being used in cancer chemotherapy. Results of pre-clinical studies also support the fact that human DNA ligases are an attractive target for the development of new anticancer agents which work by the selective inhibition of rapidly proliferating cancer cells. In this manuscript, we discuss, in brief, the structure, synthesis, structure-activity-relationship (SAR) and anticancer activity of recently reported hLigI inhibitors.

In vitro and in vivo antidiabetic effect of extracts of Melia azedarach, Zanthoxylum alatum, and Tanacetum nubigenum.

BACKGROUND: To investigate the antidiabetic effect of Himalayan Medicinal plants from India viz. Melia azedarach (Family: Meliaceae), Zanthoxylum alatum (Family: Rutaceae), Tanacetum nubigenum (Family: Asteraceae) using in-vitro as well as in-vivo approaches. METHODS: Their effects were examined on stimulation of glucose uptake by C2C12 cultured cell line, inhibitory effect on human recombinant Protein tyrosine phosphatase-1B (PTP-1B) and followed by the hypoglycaemic activity of extracts in Streptozotocin (STZ) induced diabetic rats. RESULTS: All prepared extracts had been found to enrich with polyphenolic, flavonoids, terpenoids, anthraquinones and saponins type of compounds. n-Butanol fraction of Zanthoxylum alatum showed maximum PTP-1B inhibition (61.9%) whereas ethanol extract of Tanacetum nubigenum showed strong stimulation of glucose uptake (+61.2%) in C2Cl2 myotubes. In STZ induced Sprague-Dawley rats, significant decrease in blood glucose level was observed in ethanol extract of Melia azaderach treated group as 14.8% (p < 0.01) whereas in the ethanol extract of Tanacetum nubigenum treated group, it was observed as 15.5% (p < 0.01) compare to metformin which showed 26.8% (p < 0.01) lowering of blood glucose in the same time duration of 5 h study. CONCLUSION: This study demonstrated that these plants have a significant therapeutic value in type-2-diabetes mellitus and related complications thus supporting their traditional uses in Indian traditional system of medicine.

Dithiolethiones: a privileged pharmacophore for anticancer therapy and chemoprevention.

Dithiolethiones are five-membered sulfur-containing cyclic scaffolds that exhibit antioxidative, anti-inflammatory, antithrombic and chemotherapeutic activities. Dithiolethiones display the chemopreventive and cytoprotective effects by activating the antioxidant response element and mounting the transcription of cytoprotective phase II enzymatic machinery. In addition, several classes of dithiolethiones efficiently modulate the activities of proteins that play crucial roles in normal and cancer cells, including glutathione S-transferase, cyclooxygenases and master regulator NF-κB. The present paper summarizes synthetic aspects, pharmacological potentials and biological attributes of dithiolethiones and its derivatives. Additionally, this review concludes with a discussion on how the current state-of-the-art technologies may help in defining a structure-activity relationship of dithiolethiones, thereby facilitating the design and synthesis of potent drug candidates.