Cancer is a disorder that rigorously affects the human population worldwide. There is a steady demand for new remedies to both treat and prevent this life-threatening sickness due to toxicities, drug resistance and therapeutic failures in current conventional therapies. Researchers around the world are drawing their attention towards compounds of natural origin. For decades, human beings have been using the flora of the world as a source of cancer chemotherapeutic agents. Currently, clinically approved anticancer compounds are vincristine, vinblastine, taxanes, and podophyllotoxin, all of which come from natural sources. With the triumph of these compounds that have been developed into staple drug products for most cancer therapies, new technologies are now appearing to search for novel biomolecules with anticancer activities. Ellipticine, camptothecin, combretastatin, curcumin, homoharringtonine and others are plant derived bioactive phytocompounds with potential anticancer properties. Researchers have improved the field further through the use of advanced analytical chemistry and computational tools of analysis. The investigation of new strategies for administration such as nanotechnology may enable the development of the phytocompounds as drug products. These technologies have enhanced the anticancer potential of plant-derived drugs with the aim of site-directed drug delivery, enhanced bioavailability, and reduced toxicity. This review discusses mechanistic insights into anticancer compounds of natural origins and their structural activity relationships that make them targets for anticancer treatments.

Ceriops decandra (CD) and Ceriops tagal (CT) are two traditionally used mangrove plants widely distributed along the coastal areas of South Asia, Africa, South Pacific. In this study, we evaluated the diuretic potential of aerial roots of CD, CT and assessed the effectiveness of the plants’ terpenoids enriched bioactive constituents against human carbonic anhydrase (hCA) enzyme through molecular docking. Firstly, the acute toxicity of CD and CT was evaluated in mice. In vivo diuretic activity was then studied in mice and the volume of excreted urine was measured. The urine was further examined for pH, density and Na+, K+, Cl− concentrations. From this, the saluretic, natriuretic, kaliuretic and CAI (carbonic anhydrase inhibitory) activities were calculated. Finally, total terpenoid contents (TTC) of the plant extracts were quantified and the terpenoids previously reported from both CD and CT were docked against four hCA isoforms - hCAII, hCAIV, hCAXII and hCAXIV. In the acute toxicity assessment, no sign of toxicity was found. In diuretic activity evaluation, both extracts displayed substantial increase in urine volume, with CD being at top. Concentrations of Na+, K+ and Cl− were also upsurged at a high dose of treatment (500 mg/kg). Both extracts at 500 mg/kg dose demonstrated potent saluretic, natriuretic and CAI activity. The TTC of CD was significantly higher than CT. In molecular docking analysis, greater binding affinity against hCA isoforms was demonstrated by the terpenoids reported from CD. Aerial roots of both CD and CT possess substantial diuretic activity with an inhibitory effect on CA. Here, diuretic potential as well as the total terpenoid content of CD were much greater between the two.

Cancer or uncontrolled cell proliferation is a major health issue worldwide and is the second leading cause of deaths globally. The high mortality rate and toxicity associated with cancer chemotherapy or radiation therapy have encouraged the investigation of complementary and alternative treatment methods, such as plant-based drugs. Moreover, over 60% of the anti-cancer drugs are molecules derived from plants or their synthetic derivatives. Therefore, in the present review, an attempt has been made to summarize the cytotoxic plants available in the Indian subcontinent along with a description of their bio-active components. The review covers 99 plants of 57 families as well as over 110 isolated bioactive cytotoxic compounds, amongst which at least 20 are new compounds. Among the reported phytoconstituents, artemisinin, lupeol, curcumin, and quercetin are under clinical trials, while brazilin, catechin, ursolic acid, β-sitosterol, and myricetin are under pharmacokinetic development. However, for the remaining compounds, there is little or no information available. Therefore, further investigations are warranted on these subcontinent medicinal plants as an important source of novel cytotoxic agents.

Substrate-site inhibitors of protein kinases have the potential to be selective and resistance-resilient.

The present research aimed to synthesize ketoprofen prodrugs and to demonstrate their potentiality for oral treatment to treat chronic inflammation by reducing its hepatotoxicity and gastrointestinal irritation. Methyl 2-(3-benzoyl phenyl) propanoate, ethyl 2-(3-benzoyl phenyl) propanoate and propyl 2-(3-benzoyl phenyl) propanoate was synthesized by esterification and identified by nuclear magnetic resonance (¹HNMR) and infrared (IR) spectrometric analysis. In silico SwissADME and ProTox-II analysis stated methyl derivative as ideal candidate for oral absorption, having a >30-fold LD50 value compared to ketoprofen with no hepatotoxicity. Moreover, in vivo hepatotoxicity study demonstrates that these ester prodrugs have significantly lower effects on liver toxicity compared to pure ketoprofen. Furthermore, ex vivo intestinal permeation enhancement ratio was statistically significant (* p < 0.05) compared to ketoprofen. Likewise, the prodrugs were found to exhibit not only remarkable in vitro anti-proteolytic and lysosomal membrane stabilization potentials, but also significant efficiency to alleviate pain induced by inflammation, as well as central and peripheral stimulus in mice model in vivo. These outcomes recommend that ketoprofen ester prodrugs, especially methyl derivative, can be a cost-effective candidate for prolonged treatment of chronic inflammatory diseases.

Ceriops decandra (Griff.) (CD) and Ceriops tagal (Perr.) (CT) are two mangrove plants of the Sundarbans distributed along the coastal areas of South Asia and South Pacific Africa. Traditionally, these plants are used to treat diabetes, pain, angina, hemorrhage, and ulcer. In this study, we investigated the antioxidative, antihyperglycemic, analgesic, and anti-inflammatory potential of the aerial roots of CD and CT. At first, the antioxidative potential of CD and CT ethanolic extracts were investigated qualitatively and quantitatively by 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical and hydrogen peroxide scavenging assays and by determining total antioxidant capacity. The total phenolic, flavonoid, tannin, and terpenoid contents of CD and CT were also estimated. The extracts' antihyperglycemic, analgesic, and anti-inflammatory potential were evaluated by oral glucose tolerance test, acetic acid-induced writhing test, and formaldehyde-induced paw-edema test, respectively. In vitro α-glucosidase and α-amylase enzyme inhibitory activities were also assessed. The CD and CT extracts were also analyzed using GCMS for the presence of phytochemicals. Then, molecular docking was carried out with α-glucosidase, α-amylase, cyclooxygenase-II (COX-II), 3-lipoxygenase (3-LOX) enzymes using the compounds found in GCMS analysis as well as the previously reported compounds from CD and CT. Finally, the pharmacokinetic and toxicological profiles of eight selected compounds were assessed with SwissADME and admetSAR server. In the antioxidative, antihyperglycemic, analgesic, and anti-inflammatory activity tests, CT extract showed a greater potential than CD extract. In addition, CT extract demonstrated higher α-glucosidase enzyme inhibitory activity in comparison to CD extract although CD extract exhibited better α-amylase enzyme inhibitory activity. Molecular docking studies revealed the presence of potentially bioactive compounds in both CD and CT. 2-(2-methylphenyl)-1-phenyl-(z)-1-propene of CD demonstrated good binding affinities for α-glucosidase, COX-II, and 3-LOX. In addition, 5S*,8S*,9S*,10R*,13S*)-18-hydroxy-16-nor-3-oxodolabr-4(18)-en-15-oic acid had high binding interactions for both α-glucosidase and α-amylase while 2',5,5'-tetramethyl-1,1'-biphenyl, 2-methyl-4-(3'-phenylpropyl)piperidine and decandrin C had high binding interactions for both COX-II and 3-LOX. Finally, 5S*,8S*,9S*,10R*,13S*)-18-hydroxy-16-nor-3-oxodolabr-4(18)-en-15-oic acid, decandrin C, 2-(2-methylphenyl)-1-phenyl-(z)-1-propene and 2-methyl-4-(3'-phenylpropyl)piperidine demonstrated better pharmacokinetic and toxicological properties in the ADMET analysis compared to the others. Hence it can be concluded that the present study supports the traditional usage of CD and CT for diabetes and pain and reveals the presence of bioactive phytochemicals in both.