Putative Anticancer Compounds from Plant-Derived Endophytic Fungi: A Review

Endophytic fungi are microorganisms that exist almost ubiquitously inside the various tissues of living plants where they act as an important reservoir of diverse bioactive compounds. Recently, endophytic fungi have drawn tremendous attention from researchers; their isolation, culture, purification, and characterization have revealed the presence of around 200 important and diverse compounds including anticancer agents, antibiotics, antifungals, antivirals, immunosuppressants, and antimycotics. Many of these anticancer compounds, such as paclitaxel, camptothecin, vinblastine, vincristine, podophyllotoxin, and their derivatives, are currently being used clinically for the treatment of various cancers (e.g., ovarian, breast, prostate, lung cancers, and leukemias). By increasing the yield of specific compounds with genetic engineering and other biotechnologies, endophytic fungi could be a promising, prolific source of anticancer drugs. In the future, compounds derived from endophytic fungi could increase treatment availability and cost effectiveness. This comprehensive review includes the putative anticancer compounds from plant-derived endophytic fungi discovered from 1990 to 2020 with their source endophytic fungi and host plants as well as their antitumor activity against various cell lines.

BESFA: Bioinformatics based Evolutionary, Structural & Functional Analysis of Prostrate, Placenta, Ovary, Testis, and Embryo (POTE) Paralogs

The POTE family comprises 14 paralogues and is primarily expressed in Prostrate, Placenta, Ovary, Testis, Embryo (POTE), and cancerous cells. The prospective function of the POTE protein family under physiological conditions is less understood. We systematically analyzed their cellular localization and molecular docking analysis to elucidate POTE proteins' structure, function, and Adaptive Divergence. Our result discerns that group three POTE paralogs (POTEE, POTEF, POTEI, POTEJ, and POTEKP (a pseudogene)) exhibits significant variation among other members could be because of their Adaptive Divergence. Furthermore, our molecular docking studies on POTE protein revealed the highest binding affinity with NCI-approved anticancer compounds. Additionally, POTEE, POTEF, POTEI, and POTEJ were subject to an explicit molecular dynamic simulation for 50ns. MM-GBSA and other essential electrostatics were calculated that showcased that only POTEE and POTEF have absolute binding affinities with minimum energy exploitation. Thus, this study's outcomes are expected to drive cancer research to successful utilization of POTE genes family as a new biomarker, which could pave the way for the discovery of new therapies.

Green Approaches of Flavonoids in Cancer: Chemistry, Applications, Management, Healthcare and Future Perspectives

In epidemiologic research, a cancer preventive benefit from plant-derived meals has been discovered with unusual consistency. However, identifying individual components responsible for this effect has been difficult. The polyphenols phytochemicals have been found to have biological activity, and they may work together to prevent cancer. Cancer is a significant public health concern in both developed and developing countries. Celery, chamomile, Ginkgo biloba, mint, red paper plants synthesized anticancer agents like taxol, irinotecan, camptothecin, topotecan, and vinblastine, vincristine, etoposide being used in clinical trials. In addition, Flavopiridol, roscovitine, combretastatin A-4, betulinic acid, and silvestrol are promising anticancer compounds. Flavonoids in vegetables, fruits, roots, and stems have demonstrated a wide range of anticancer properties, including modulating ROS, scavenging enzyme activities, participating in cell cycle arrest inducing apoptosis autophagy, and suppressing growth of tumour cell and invasiveness. This review highlighted flavonoids, cancer cell mechanism of action, applications in tumour management, and future perspectives. This review may play a significant role for industrialists and scientists working in this field.

Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets

Cancer is a complex group of diseases initiated by abnormal cell division with the potential of spreading to other parts of the body. The advancement in the discoveries of omics and bio- and cheminformatics has led to the identification of drugs inhibiting putative targets including vascular endothelial growth factor (VEGF) family receptors, fibroblast growth factors (FGF), platelet derived growth factors (PDGF), epidermal growth factor (EGF), thymidine phosphorylase (TP), and neuropeptide Y4 (NY4), amongst others. Drug resistance, systemic toxicity, and drug ineffectiveness for various cancer chemo-treatments are widespread. Due to this, efficient therapeutic agents targeting two or more of the putative targets in different cancer cells are proposed as cutting edge treatments. Heterocyclic compounds, both synthetic and natural products, have, however, contributed immensely to chemotherapeutics for treatments of various diseases, but little is known about such compounds and their multimodal anticancer properties. A compendium of heterocyclic synthetic and natural product multitarget anticancer compounds, their IC50, and biological targets of inhibition are therefore presented in this review.

Current developments in the Pyran-Based Analogues as Anticancer Agents

: Heterocyclic compounds offer an enormous area for new lead molecules for drug discovery. Till today, efforts are being continuously made to find appropriate treatment for the management of the deadly disease of cancer. Amongst the large number of heterocycles that are found in nature, heterocycles having oxygen obtained noteworthy attention due to their distinctive and pharmacological activities.‘Pyran’ is one of the most significant non-aromatic, six-membered ring composed of one oxygen atom and five carbon atoms. It is considered a privileged structure since pyran and its related derivatives exhibit a wide spectrum of biological activities. Pyran derivatives are found to have excellent anti-cancer properties against various types of cancer. The present review focussed on the current advances in different types of pyran-based derivatives as anti-cancer agents. Various in-vitro (cell based testing), in-vivo (animal based testing) models as well as molecular docking along with results are also covered. A subsection describing briefly natural pyran containing anticancer compounds is also incorporated in the review.

Barnase-Barstar Pair: Contemporary Application in Cancer Research and Nanotechnology

Barnase is an extracellular ribonuclease secreted by Bacillus amyloliquefaciens that was originally studied as a small stable enzyme with robust folding. The identification of barnase intracellular inhibitor barstar led to the discovery of an incredibly strong protein-protein interaction. Together, barnase and barstar provide a fully genetically encoded toxin-antitoxin pair having an extremely low dissociation constant. Moreover, compared to other dimerization systems, the barnase-barstar module provides the exact one-to-one ratio of the complex components and possesses high stability of each component in a complex and high solubility in aqueous solutions without self-aggregation. The unique properties of barnase and barstar allow the application of this pair for the engineering of different variants of targeted anticancer compounds and cytotoxic supramolecular complexes. Using barnase in suicide gene therapy has also found its niche in anticancer therapy. The application of barnase and barstar in contemporary experimental cancer therapy is reflected in the review.

Quercetin Impact in Pancreatic Cancer: An Overview on Its Therapeutic Effects

Pancreatic cancer (PC) is a lethal malignancy cancer, and its mortality rates have been increasing worldwide. Diagnosis of this cancer is complicated, as it does not often present symptoms, and most patients present an irremediable tumor having a 5-year survival rate after diagnosis. Regarding treatment, many concerns have also been raised, as most tumors are found at advanced stages. At present, anticancer compounds-rich foods have been utilized to control PC. Among such bioactive molecules, flavonoid compounds have shown excellent anticancer abilities, such as quercetin, which has been used as an adjunctive or alternative drug to PC treatment by inhibitory or stimulatory biological mechanisms including autophagy, apoptosis, cell growth reduction or inhibition, EMT, oxidative stress, and enhancing sensitivity to chemotherapy agents. The recognition that this natural product has beneficial effects on cancer treatment has boosted the researchers’ interest towards more extensive studies to use herbal medicine for anticancer purposes. In addition, due to the expensive cost and high rate of side effects of anticancer drugs, attempts have been made to use quercetin but also other flavonoids for preventing and treating PC. Based on related studies, it has been found that the quercetin compound has significant effect on cancerous cell lines as well as animal models. Therefore, it can be used as a supplementary drug to treat a variety of cancers, particularly pancreatic cancer. This review is aimed at discussing the therapeutic effects of quercetin by targeting the molecular signaling pathway and identifying antigrowth, cell proliferation, antioxidative stress, EMT, induction of apoptotic, and autophagic features.

A Review on Diversity of Anticancer Compounds Derived from Indonesian Marine Sponges

As a tropical archipelago country, Indonesia has a mega diversity of marine organisms, such as sponges. About 850 species of sponges were identified from the east part of Indonesia. The uniqueness of Indonesian marine sponges attracted many researchers to explore the sponge’s potential in producing active substances. During 1995-2016, about 40 genera of Indonesian sponges were investigated for their potential in producing pharmacological activity such as antimicrobial, anticancer, antivirus, multidrug-resistant (MDR), etc. The data showed that 56.7% of 430 reported compounds were confirmed as new compounds. The research trend on Indonesian sponges was high during 2004-2013, but decreasing after 2014. However, researches in the term of active substances from marine sponges should find provide the basic skeleton of anti-cancer drug lead compounds. Chemical structure diversity plays an important role in the exploration of anticancer lead compounds. The purpose of this paper is to review the potential of anticancer diversity compounds derived from Indonesian sponges, to get comprehensive data for further investigation. As the conclusion of our review, the most anticancer compounds derived from Indonesian marine invertebrates are alkaloid groups (such as aaptamine, manzamine, and bromopyrrole derivatives), then terpenoid groups (such as diterpene, coelodiol, and coeloic acid, sesquiterpene aminoquinone, and also (+)-curcuphenol and (+)-curcudiol), and also from the other groups such as sterole, peptide, polyketide, amino acid derivatives, natural organic acid, and quinone. The most effective anticancer compounds were 5-benzoyldemethylaaptamine, isoaaptamine, 3-bromofascaplysin, hyrtioreticulins A, stylissamide X, sigmosceptrellin B, and diacarperoxide S.