Repurposing FDA approved drugs against monkeypox virus DNA dependent RNA polymerase: virtual screening, normal mode analysis and molecular dynamics simulation studies.

Zoonotic monkeypox disease, caused by the double-stranded DNA monkeypox virus, has become a global concern. Due to the absence of a specific small molecule drug for the disease, this report aims to identify potential inhibitor drugs for monkeypox. This study explores a drug repurposing strategy using virtual screening to evaluate 1615 FDA approved drugs against the monkeypox virus DNA dependent RNA polymerase subunit A6R. Normal mode analysis and molecular dynamics simulation assessed the flexibility and stability of the target protein in complex with the top screened drugs. The analysis identified Nilotinib (ZINC000006716957), Conivaptan (ZINC000012503187), and Ponatinib (ZINC000036701290) as the most potential RNA polymerase inhibitors with binding energies of - 7.5 kcal/mol. These drugs mainly established hydrogen bonds and hydrophobic interactions with the protein active sites, including LEU95, LEU90, PRO96, MET110, and VAL113, and residues nearby. Normal mode analysis and molecular dynamics simulation confirmed the stability of interactions between the top drugs and the protein. In conclusion, we have discovered promising drugs that can potentially control the monkeypox virus and should be further explored through experimental assays and clinical trials to assess their actual activity against the disease. The findings of this study could lay the foundation for screening repurposed compounds as possible antiviral treatments against various highly pathogenic viruses.

Theabrownin: a dietary nutraceutical with diverse anticancer mechanisms.

Cancer, a highly deadly disease, necessitates safe, cost-effective, and readily accessible treatments to mitigate its impact. Theabrownin (THBR), a polyphenolic pigment found in Pu-erh tea, has garnered attention for its potential benefits in memory, liver health, and inflammation control. By observing different biological activities of THBR, recently researchers have unveiled THBR's promising anticancer properties across various human cancer types. By examining existing studies, it is evident that THBR demonstrates substantial potential in inhibiting cell proliferation and reducing tumour size with minimal harm to normal cells. These effects are achieved through the modulation of key molecular markers such as Bcl-2, Bax, various Caspases, Poly (ADP-ribose) polymerase cleavage (Cl-PARP), and zinc finger E box binding homeobox 1 (ZEB 1). This review aims to provide in-depth insights into THBR's role in cancer research. This review also elucidates the underlying anticancer mechanisms of THBR, offering promise as a novel anticancer drug to alleviate the global cancer burden.

Alpinetin: a Dietary Flavonoid with Diverse Anticancer Effects.

Cancer is a global burden and mechanistically complex disease with a plethora of genetic, physiological, metabolic, and environmental alterations. The development of dietary nutraceuticals into cancer chemotherapeutics has emerged as a new paradigm in cancer treatment. Alpinetin (ALPI) is a novel flavonoid component of multiple edible and medicinal plants and possesses a wide range of biological and pharmacological activities including antibacterial, anti-hemostatic, anti-oxidative, anti-hepatotoxic, stomachic, immunosuppressive, and anti-inflammatory. Recently, ALPI has been reported as a bioactive dietary nutraceutical with promising anticancer activity in various human cancers through multiple mechanisms. The purpose of this review is to compile the data on natural sources of ALPI, and its anticancer activity including cellular targets and anticancer mechanism in various human cancers. Moreover, this review will set the stage for further design and conduct pre-clinical and clinical trials to develop ALPI into a lead structure for oncological therapy.

Vitamin K: A novel cancer chemosensitizer.

Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.

A comprehensive review on anticancer mechanism of bazedoxifene.

Cancer is counted as a second leading cause of death among nontransmissible diseases. Identification of novel anticancer drugs is therefore necessary for the effective treatment of cancer. Conventional drug discovery is time consuming and expensive process. Unlike conventional drug discovery, drug repositioning offers a novel strategy for urgent drug discovery since it is a cost-effective and faster process. Bazedoxifene (BZA) is a synthetic selective estrogen receptor modulator, approved by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women. BZA is now being studied for its anticancer activity in various cancers including breast cancer, liver cancer, pancreatic cancer, colon cancer, head and neck cancer, medulloblastoma, brain cancer, and gastrointestinal cancer. Studies have reported that BZA is effective in reducing cancer progression through multiple mechanisms. BZA could effectively inhibit STAT3, PI3K/AKT, and MAPK signaling pathways and induce apoptosis. In addition to its anticancer activity as monotherapy, BZA has been shown to enhance the chemotherapeutic efficacy of clinical drugs such as paclitaxel, cisplatin, palbociclib, and oxaliplatin in multiple neoplasms. This review mainly focused on the anticancer activity, cellular targets, and anticancer mechanism of BZA, which may help the further design and conduct of research and repositioning it for oncological clinic trials.