Current Topics in Medicinal Chemistry - Volume 21, Issue 15, 2021

Cancer is one of the major causes of death in human beings. While traditional cancer treatments kill cancerous cells, they negatively affect normal cells. In addition, the side effects and high medical costs of treatment prevent effective management of cancer. Nonetheless, anticancer peptides have gained popularity over the recent years as potential therapeutic agents that may complement traditional therapies. Compared to conventional wet-lab experiments, computation-based methods provide a promising platform for high-throughput identification of peptides that have anticancer activity. Therefore, this review summarizes the currently available databases for anticancer peptides/proteins. This is a survey of 22 recently published in-silico methods that aim to predict anticancer peptides accurately. More specifically, the article details the benchmark datasets, feature construction, feature selection, machine learning algorithms, assessment criteria, comparison of different methods, and publicly available predictors. We also compare the prediction performance of these predictors to the benchmark dataset. Finally, the study makes several recommendations concerning the future development of databases for anticancer peptides and methods that can be used to predict anticancer peptides.

Efficacious treatment for breast cancer is still a challenge despite the presence of various treatment options. Aromatase enzyme present in the breast tissue is responsible for estrogen formation from androgens. Aromatase inhibitors manifest remarkably ameliorated therapeutic efficacy as compared to the current therapeutic options available and exhibit a better safety profile as compared to the other drugs. Clinical resistance to aromatase inhibitors is perceived as a lack of growth inhibition by aromatase inhibitors treatment and cancer therapy becomes ineffective in causing a decrease in the size of the tumor. Naturally extracted aromatase inhibitors have a huge positive impact on vitality and living standards. This review article highlights the particulars of the currently approved steroidal and non-steroidal aromatase inhibitors for clinical use, adverse effects associated with their use and approach to tackling the problem, various strategies to overcome aromatase inhibitors resistance, information on the synthesis of various peculiar aromatase inhibitors which can prove as highly efficient and potent drugs in the near future and the drugs of natural and semi-synthetic origin which can demonstrate to be more efficient, potent and less-toxic than conventional therapy.

Background: The novel strain SARS-CoV-2 of coronavirus diseases (COVID-19) became pandemic at the end of 2019 with an unprecedented global crisis by infecting around 11 million people in more than 200 countries. The condition has now been provoked by the demand, supply, and liquidity shocks that COVID-19 has attacked the lives of a vast population. Objectives: Researchers are therefore trying to encode and understand the viral genome sequence along with various potential targets to explore the transmission mechanism and the mode of treatment for COVID-19. The important structural proteins such as nucleocapsid protein (N), membrane protein (M), an envelope protein (E), and spike protein (S) related to COVID-19 are discussed in this manuscript. Methods: The topology of these various targets has been explored utilizing structure-based design and crystallographic studies. Results: The literature reported that the N-protein processes the viral genome to the host cell during replication. The “N-terminal domain” and “C-terminal domain” contribute towards localization in the endoplasmic region and dimerization respectively. The M protein determines the shape of coronavirus and also assists the S protein to integrate with the Golgi-endoplasmic region complex leading to the stabilization of the virion. The smallest hydrophobic viroporin termed “E” takes part in morphogenesis and pathogenesis during intracellular infection. The viral spike (S) protein attaches the cellular receptors and initiates virus-cell membrane fusions. The main protease in the proteolytic process during viral gene expression and replication has also been discussed. Conclusion: Currently, there is no permanent cure and treatment of COVID-19 hence researchers are repurposing a suitable combination of drugs including antiviral, antimalarial, antiparasitic, and antibacterial, hypertensive receptor blockers, immunosuppressants, anti-arthritis drugs, including ayurvedic formulations. In brief, it is justified that, for complete recovery, there is a need for deep and elaborate studies on genomic sequences and invading mechanisms in the host cell.

Nanotechnology has shown promising advancements in the field of drug development and its delivery. In particular, the applications of nanoparticles for treatment and diagnostics of cancer reached such a precision that it can detect a single cancer cell and target it to deliver a payload for the treatment of that cancerous cell. Conventional cancer therapy methods have side effects, and diagnostics techniques are time-consuming and expensive. Nanoparticles (NPs) such as polymeric nanoparticles (nanogels, nanofibers, liposomes), metallic nanoparticles such as gold NP (GNPs), sliver NP (AgNP), calcium nanoparticles (CaNPs), carbon nanotubes (CNTs), graphene, and quantum dots (QDs) have revolutionized cancer diagnostics and treatments due to their high surface charge, size, and morphology. Functionalization of these nanoparticles with different biological molecules, such as antibodies, helps them to target delivery and early detection of cancer cells through their plasmon resonance properties. While some of the magnetic properties of nanoparticles such as iron (Fe), copper (Cu), and carbon NT were also evaluated for detection and treatments of cancer cells. An advanced type of nanoparticles, such as nanobubbles and oxygen-releasing polymers, are helping to address the hypoxia conditions in the cancer microenvironment, while others are employed in photodynamic therapy (PDT) and photothermal therapy (PTT) due to their intrinsic theranostic properties. The green synthesis of nanoparticles has further increased biocompatibility and broadened their applications. In this review paper, we discussed the advancement in nanotechnology and its applications for cancer treatment and diagnostics and highlighted challenges for translation of these advanced nano-based techniques for clinical applications and their green synthesis.

Cancer is a kind of human cell degenerative disease that has affected many people for several years. Cancer is caused due to the abnormal growth of cells in every particular part of the body. The 1,3,4-oxadiazole ring is found to be a binding moiety that has anticancer potential. Various works on the 1,3,4-oxadiazole moiety showing anticancer activity have been reported. The present analysis summarizes general synthetic methods for 1,3,4 oxadiazole. Different receptors on which these drug acts are discussed. This review also presents pharmacophore models for topoisomerase-I, histone deacetylase, and epidermal growth factor enzymes.

Background: Flavonolignans like silybin, hydnocarpin, and siliandrin are a group of natural compounds combining the structural moieties of flavonoid and phenylpropanoid (lignan). Hydnocarpin and silandrin have been less explored because of their trace occurrence in nature. Objective: The present study aimed at chemical conversion of silybin to hydnocarpin and siliandrin. Another objective was to synthesize a series of amide derivatives and biologically evaluate them with regard to their anti-cancer effects. Methods: In order to selectively convert silybin to 23-iodo silybin, 23-iodo hydnocarpin D and 23- iodo isosilandrin, the ratio of Ph3P, imidazole and molecular iodine was meticulously adjusted. These three iodide compounds were converted into amide compounds by chemical transformation. MTT method was applied to evaluate their anti-cancer potency. The binding affinity to related proteins was calculated by molecular docking. Results: A total of 45 new amido-derivatives were synthesized and structurally characterized by NMR and HRMS. Some of them showed moderate to good antiproliferative potency against cancer cells. The activity of compound 10j was further testified by colony formation assay and molecular docking. Conclusion: The synthesis of 23-iodo silybin, 23-iodo hydnocarpin D and 23-iodo isosilandrin from silybin was successfully accomplished by one simple iodination reaction. Some of the amide derivatives of sylibin/hydnocarpin D /silandrin exhibited a remarkable inhibitory effect of proliferation on cancer cells compared to silybin. These results would pave the way for further investigation on the derivatives of flavonolignans for the treatment of cancer.

Background: Low therapeutic efficacy and drug-induced systemic toxicity of currently used anti-cancerous chemotherapeutic agents are major compelling factors for finding out clinically efficient molecules with high efficiency and less toxicity. Objective: The current research work was undertaken to evaluate the anticancer potential of Myricanol- 9-acetate (MA), a novel naturally occurring derivative of myricanol. Methods: MCF-7, MiaPaCa-2, and HCT 116 were used for cytotoxicity determination of the MA and ML (Myricanol) by MTT assay. The mechanistic study involved the determination of cell cycle arrest, Δψm loss, ROS generation, western blot assay, flow cytometry by reported methods on MCF-7 cells. Results: MA exhibited anticancer activity against all three cell lines, however, the molecule was found most active against the MCF-7 cell line. We observed IC5020 μM with MA treatment as compared to the IC50 of 42 μM for myricanol treatment. Detailed mechanistic studies revealed that MA induces apoptosis of MCF-7 cell line through ROS generation and dose-dependent drop in mitochondrial membrane potential associated with cell cycle arrest at G0/G1 phase. Our results further demonstrated that down-regulation of Bcl2 and activation of the caspase cascade are the events involved in the MA-induced apoptosis. Flow cytometry results indicated an increase in early and late apoptotic population in a dose-dependent manner with an apoptotic population of about 20% at 30 μM of MA, thus, supporting our results. Conclusion: Present findings suggest that MA might serve as a promising novel drug candidate with high scope for taking it to further evaluation in preclinical and clinical studies.