Natural products play a pivotal role in medicine especially in the cancer arena. Many drugs that are currently used in cancer chemotherapy originated from or were inspired by nature. Jerantinine B (JB) is one of seven novel Aspidosperma indole alkaloids isolated from the leaf extract of Tabernaemontana corymbosa. Preliminary antiproliferative assays revealed that JB and JB acetate significantly inhibited growth and colony formation, accompanied by time- and dose-dependent apoptosis induction in human cancer cell lines. JB significantly arrested cells at the G2/M cell cycle phase, potently inhibiting tubulin polymerisation. Polo-like kinase 1 (PLK1; an early trigger for the G2/M transition) was also dose-dependently inhibited by JB (IC50 1.5 µM). Furthermore, JB provoked significant increases in reactive oxygen species (ROS). Annexin V+ cell populations, dose-dependent accumulation of cleaved-PARP and caspase 3/7 activation, and reduced Bcl-2 and Mcl-1 expression confirm apoptosis induction. Preclinical in silico biopharmaceutical assessment of JB calculated rapid absorption and bioavailability >70%. Doses of 8-16 mg/kg JB were predicted to maintain unbound plasma concentrations >GI50 values in mice during efficacy studies. These findings advocate continued development of JB as a potential chemotherapeutic agent.

Cardamonin is a natural chalcone that has been shown to exhibit high anticancer activity. In an attempt to discover analogues of cardamonin with enhanced anticancer activity, 19 analogues were synthesized and tested against A549 and HK1 cell lines. Results of the MTS cell viability assay showed that several derivatives possessed cytotoxic activities that were several-fold more potent than cardamonin. SAR analysis showed the importance of the ketone and alkene groups for bioactivity, while substituting cardamonin's phenolic groups with more polar moieties resulted in activity enhancement. As part of the SAR study and further exploration of chemical space, the effect of metal coordination on cytotoxicity was also investigated, but it was only possible to successfully obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active analogue possessing IC values of 13.2μM and 0.7μM against A549 and HK1 cells, corresponding to a 5- and 32-fold increase in activity, respectively. It was also able to significantly inhibit the migration of A549 and HK1 cells. Further mode of action studies have shown that the most active analogue, 19, induced DNA damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These events further led to the induction of apoptosis by the compound via caspase-3/7 and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression. Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which indicated that it exerted its anticancer activity, at least in part, via inhibition of the mTOR signalling pathway.

The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (−)-jerantinines A and E from sustainably sourced (−)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (−)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin—(−)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.

Introduction: Peptic lesions usually develop when there is an imbalance between aggressive drivers and gastro-protective mediators that guard the lining of the gastrointestinal tract. The most crucial of these mediators are antioxidants, whose loss may predispose to oxidative stress, which is believed to be the main aggravator of several diseases including peptic ulcer. Proton pump inhibitors (PPIs) are drugs that are highly effective and widely used for therapeutic management of peptic disorders through inhibition of gastric acid secretion. In spite of this, oxidative damage may continue to be a major issue that can predispose to future lesions. Objective: The present study is designed to explore the possible antioxidant capability of different PPIs, including omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, in an aim to suggest an agent that, in addition to its acid-suppression properties, can provide antioxidant profit. Methods: The antioxidant activity of different PPIs was evaluated calorimetrically to test the ability of each drug to quench oxygen free radical, using the well-known stable free radical α,α-diphenyl-β-picrylhydrazyl (DPPH), and compared to ascorbic acid (AA; vitamin C). The measurements were performed using a spectrophotometer at 517 nm. Results: All the studied drugs reduced DPPH, but to different extents. However, omeprazole and esomeprazole showed the highest ability to scavenge free radicals (50% inhibitory concentrations [IC 50 s] of the percentage for free radical scavenging activity are 18.7 ± 5.7 and 18.7 ± 5.7, respectively, and the AA equivalents are 83,772 ± 11,887 and 81,732 ± 8,523 mg AA/100 g, respectively). Conversely, lansoprazole, pantoprazole, and rabeprazole might be having no role in this story (IC 50 s of the percentage for free radical scavenging activity are 49.3 ± 3.1, 49 ± 9.4, and 40.7 ± 7.2, respectively, and the AA equivalents are 30,458 ± 3,884, 32,222 ± 10,377, and 37,876 ± 8,816 mg AA/100 g, respectively). Conclusion: Thus, omeprazole and esomeprazole may confer a significant dual action in gastrointestinal protection by providing potent antioxidant properties in addition to their major role as acid-suppression agents. However, further studies are essential to elucidate the mechanism behind the difference between the drugs of the same class.

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Peptic ulcer (P.U.) is the gastrointestinal tract's most frequent disorder affecting mainly the stomach and duodenum. Surgical intervention, ingested materials and microbial infections may trigger inflammation that further predispose to oxidative stress. Proton pump inhibitors (PPIs) are group of compounds established for suppressions of gastric acid secretions profoundly and permanently over a reasonably long period of time. Oxidative stress has been shown to be involved in the pathophysiology of various diseases and disorders, including P.U. Particularly when H. pylori infection accompanies it. In addition to the colonization of this microorganism, gastric mucosa may be subjected to extreme oxidative stress with large levels of inflammatory cell aggregation, which may eventually predispose to the disorder. PPIs exert several effects other than gastric acid suppression that can be used to treat Helicobacter pylori infections, disorders of the respiratory tract, viral infections, and other conditions related to dysfunction of endothelium by activating endogenous antioxidant protection and reducing the release of cytokine. Recent therapeutic protocols have recommended PPIs as gastro-protective compounds not only because of their acid suppression properties, but also because of their potent antioxidant and anti-inflammatory properties. Keywords: Proton Pump Inhibitors, Peptic Ulcer, Oxidative Stress, H. pylori

Allergic rhinitis (AR) is a type of inflammatory condition that includes a group of symptoms, mainly affecting the nasal mucosa. Nasal obstruction, sneezing, stuffy or runny nose, in addition to swollen, itchy, red and watery eyes are the most common symptoms of the disease. These symptoms are triggered as a result of increased inflammatory mediators such as histamine and leukotrienes. Studies have recently shown the role of vitamin D (vit.D) in many allergic and immune conditions, where receptors for the active form of vit.D (1,25-dihydroxyvitamin D3) have been discovered on the surface of almost all types of inflammatory cells. Therefore, the present study was conducted to explore the level of vit. D in AR patients and its correlation with the severity of the disease. Two groups participated in the study; the first group included 49 patients who were diagnosed in a private otolaryngology clinic by the first author as having allergic rhinitis (AR group). The second one served as a control group and included 50 apparently healthy volunteers with no history of AR. The mean level of IgE and vit. D was found to be 326.3 and 10.2 ng/ml in the AR group, respectively, and 30.8 and 23.3 ng/ml in the control group, respectively. Ninety-three percent of AR patients have shown a deficiency in vit. D level, where 56% of this group showed severe deficiency. On the other hand, 34% of the control group has shown an insufficient level of vit. D. Additionally, 64% of AR patients have shown serum levels of IgE at values ranging between 100-299 ng/ml. Higher serum levels of IgE at values ranging between 300-599 ng/ml and 600-1000 ng/ml were observed in 25% and 11% of AR patients, respectively. The prevalence of low levels of vit. D in the AR group was significantly higher than that in the control group (P < 0.001). Vit. D deficiency is significantly related to severe AR symptoms and measuring serum vit. D level is recommended in the management plan of this group of patients.