Piperazin incorporated Schiff Base derivatives: Assessment of in vitro biological activities, metabolic enzyme inhibition properties, and molecular docking calculations.

The cytotoxic activities of the compounds were determined by the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) method in human breast cancer (MCF-7), human cervical cancer (HeLa), and mouse fibroblast (L929) cell lines. The compounds MAAS-5 and four modified the supercoiled tertiary structure of pBR322 plasmid DNA. MAAS-5 showed the highest cytotoxic activity in HeLa, MCF-7, and L929 cells with IC50 values of 16.76 ± 3.22, 28.83 ± 5.61, and 2.18 ± 1.22 µM, respectively. MAAS-3 was found to have almost the lowest cytotoxic activities with the IC50 values of 93.17 ± 9.28, 181.07 ± 11.54, and 16.86 ± 6.42 µM in HeLa, MCF-7, and L929 cells respectively at 24 h. Moreover, the antiepileptic potentials of these compounds were investigated in this study. To this end, the effect of newly synthesized Schiff base derivatives on the enzyme activities of carbonic anhydrase I and II isozymes (human carbonic anhydrase [hCA] I and hCA II) was evaluated spectrophotometrically. The target compounds demonstrated high inhibitory activities compared with standard inhibitors with Ki values in the range of 4.54 ± 0.86-15.46 ± 8.65 nM for hCA I (Ki value for standard inhibitor = 12.08 ± 2.00 nM), 1.09 ± 0.32-29.94 ± 0.82 nM for hCA II (Ki value for standard inhibitor = 18.22 ± 4.90 nM). Finally, the activities of the compounds were compared with the Gaussian programme in the B3lyp, HF, M062X base sets with 6-31++G (d,p) levels. In addition, the activities of five compounds against various breast cancer proteins and hCA I and II were compared with molecular docking calculations. Also, absorption, distribution, metabolism, excretion, and toxicity analysis was performed to investigate the possibility of using five compounds as drug candidates.

Natural antioxidants from some fruits, seeds, foods, natural products, and associated health benefits: An update.

Antioxidants are compounds that inhibit the oxidation of other molecules and protect the body from the effects of free radicals, produced either by normal cell metabolism or as an effect of pollution and exposure to other external factors and are responsible for premature aging and play a role in cardiovascular disease. degenerative diseases such as cataracts, Alzheimer's disease, and cancer. While many antioxidants are found in nature, others are obtained in synthetic form and reduce oxidative stress in organisms. This review highlights the pharmacological relevance of antioxidants in fruits, plants, and other natural sources and their beneficial effect on human health through the analysis and in-depth discussion of studies that included phytochemistry and their pharmacological effects. The information obtained for this review was collected from several scientific databases (ScienceDirect, TRIP database, PubMed/Medline, Scopus, Web of Science), professional websites, and traditional medicine books. Current pharmacological studies and evidence have shown that the various natural antioxidants present in some fruits, seeds, foods, and natural products have different health-promoting effects. Adopting functional foods with high antioxidant potential will improve the effective and affordable management of free radical diseases while avoiding the toxicities and unwanted side effects caused by conventional medication.

The effects of thymoquinone on pancreatic cancer: Evidence from preclinical studies.

Thymoquinone (TQ) is a secondary metabolite found in abundance in very few plant species including Nigella sativa L., Monarda fistulosa L., Thymus vulgaris L. and Satureja montana L. Preclinical pharmacological studies have shown that TQ has many biological activities, such as anti-inflammatory, antioxidant and anticancer. Both in vivo and in vitro experiments have shown that TQ acts as an antitumor agent by altering cell cycle progression, inhibiting cell proliferation, stimulating apoptosis, inhibiting angiogenesis, reducing metastasis and affecting autophagy. In this comprehensive study, the evidence on the pharmacological potential of TQ on pancreatic cancer is reviewed. The positive results of preclinical studies support the view that TQ can be considered as an additional therapeutic agent against pancreatic cancer. The possibilities of success for this compound in human medicine should be further explored through clinical trials.

Diosgenin: An Updated Pharmacological Review and Therapeutic Perspectives.

Plants including Rhizoma polgonati, Smilax china, and Trigonella foenum-graecum contain a lot of diosgenin, a steroidal sapogenin. This bioactive phytochemical has shown high potential and interest in the treatment of various disorders such as cancer, diabetes, arthritis, asthma, and cardiovascular disease, in addition to being an important starting material for the preparation of several steroidal drugs in the pharmaceutical industry. This review aims to provide an overview of the in vitro, in vivo, and clinical studies reporting the diosgenin's pharmacological effects and to discuss the safety issues. Preclinical studies have shown promising effects on cancer, neuroprotection, atherosclerosis, asthma, bone health, and other pathologies. Clinical investigations have demonstrated diosgenin's nontoxic nature and promising benefits on cognitive function and menopause. However, further well-designed clinical trials are needed to address the other effects seen in preclinical studies, as well as a better knowledge of the diosgenin's safety profile.

Evaluation of mutagenesis, necrosis and apoptosis induced by omeprazole in stomach cells of patients with gastritis.

BACKGROUND: Gastritis is a superficial and prevalent inflammatory lesion that is considered a public health concern once can cause gastric ulcers and gastric cancer, especially when associated with Helicobacter pylori infection. Proton pump inhibitors, such as omeprazole, are the most widely used drugs to treat this illness. The aim of the study was evaluate cytogenetic effects of omeprazole in stomach epithelial cells of patients with gastritis in presence and absence of H. pylori, through cytogenetic biomarkers and catalse and superoxide dismutase analysis. METHODS: The study included 152 patients from the Gastroenterology Outpatient Clinic of Hospital Getúlio Vargas, Teresina-Brazil, that reported continuous and prolonged omeprazole use in doses of 20, 30 and 40 mg/kg. The participants were divided into groups: (1) patients without gastritis (n = 32); (2) patients without gastritis but with OME use (n = 24); (3) patients with gastritis (n = 26); (4) patients with gastritis undergoing OME therapy (n = 26); (5) patients with gastritis and H. pylori (n = 22) and (6) patients with gastritis and H. pylori on OME therapy (n = 22). RESULTS: OME induced cytogenetic imbalance in the stomach epithelium through the formation of micronuclei (group 6 > 1, 2, 3, 4, 5; group 5 > 1, 2, 3; group 4 > 1, 2, 3); bridges (groups 4 and 6 > 1, 2, 3, 5 and group 2 > 3, 5); buds (groups 2,4,6 > , 1, 3, 5); binucleated cells (group 6 > 1, 2, 3, 4, 5; group 4 > 1, 2, 3); (groups 2 and 3 > 1); picnoses (group 6 > 1, 2, 3, 4, 5), groups 2 and 5 > 1, 3; group 4 > 1, 2, 3, 5); cariorrexis (groups 6 and 4 > 1, 2, 3, 5; groups 2, 3, 5 > 1) and karyolysis (groups 2, 4, and 6 > 1, 3, 5; groups 3 and 5 > 1). The OME cytogenetic instability was associated with H. pylori infection, indicating clastogenic/aneugenic effects, chromosomes alterations, gene expression changes, cytotoxicity and apoptosis. CONCLUSIONS: The cytogenetic changescan be attributed to several mechanisms that are still unclear, including oxidative damage, as observed by increased catalase and superoxide dismutase expresion. Positive correlations between antioxidant enzymes were found with micronuclei formation, and were negative for picnoses. Thus, the continuous and prolonged omeprazole use induces genetic instability, which can be monitored through cytogenetic analyzes, as precursor for gastric cancer.

Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential.

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.

Urtica dioica-Derived Phytochemicals for Pharmacological and Therapeutic Applications.

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value.

Nutraceutical Profiling, Bioactive Composition, and Biological Applications of Lepidium sativum L.

The roots, leaves, and seeds of Lepidium sativum L., popularly known as Garden cress in different regions, have high economic importance; although, the crop is particularly cultivated for the seeds. In traditional medicine, this plant has been reported to possess various biological activities. This review is aimed at providing updated and critical scientific information about the traditional, nutritional, phytochemical, and biological activities of L. sativum. In addition, the geographic distribution is also reviewed. The comprehensive literature search was carried out with the help of different search engines PubMed, Web of Science, and Science Direct. This review highlighted the importance of L. sativum as an edible herb that possesses a wide range of therapeutic properties along with high nutritional values. Preclinical studies (in vitro and in vivo) displayed anticancer, hepatoprotective, antidiabetic, hypoglycemic, antioxidant, antimicrobial, gastrointestinal, and fracture/bone healing activities of L. sativum and support the clinical importance of plant-derived bioactive compounds for the treatment of different diseases. Screening of literature revealed that L. sativum species and their bioactive compounds may be a significant source for new drug compounds and also could be used against malnutrition. Further clinical trials are needed to effectively assess the actual potential of the species and its bioactive compounds.

In Silico Screening of Natural Products as Potential Inhibitors of SARS-CoV-2 Using Molecular Docking Simulation.

OBJECTIVE: To explore potential natural products against severe acute respiratory syndrome coronavirus (SARS-CoV-2) via the study of structural and non-structural proteins of human coronaviruses. METHODS: In this study, we performed an in-silico survey of 25 potential natural compounds acting against SARS-CoV-2. Molecular docking studies were carried out using compounds against 3-chymotrypsin-like protease (3CLPRO), papain-like protease (PLPRO), RNA-dependent RNA polymerase (RdRp), non-structural protein (nsp), human angiotensin converting enzyme 2 receptor (hACE2R), spike glycoprotein (S protein), abelson murine leukemia viral oncogene homolog 1 (ABL1), calcineurin-nuclear factor of activated T-cells (NFAT) and transmembrane protease serine 2. RESULTS: Among the screened compounds, amentoflavone showed the best binding affinity with the 3CLPRO, RdRp, nsp13, nsp15, hACE2R. ABL1 and calcineurin-NFAT; berbamine with hACE2R and ABL1; cepharanthine with nsp10, nsp14, nsp16, S protein and ABL1; glucogallin with nsp15; and papyriflavonol A with PLPRO protein. Other good interacting compounds were juglanin, betulinic acid, betulonic acid, broussooflavan A, tomentin A, B and E, 7-methoxycryptopleurine, aloe emodin, quercetin, tanshinone I, tylophorine and furruginol, which also showed excellent binding affinity towards a number of target proteins. Most of these compounds showed better binding affinities towards the target proteins than the standard drugs used in this study. CONCLUSION: Natural products or their derivatives may be one of the potential targets to fight against SARS-CoV-2.

Hepatoprotective Screening of Seriphidium kurramense (Qazilb.) Y.R. Ling.

Investigation on medicinal plants' therapeutic potential has gained substantial importance in the discovery of novel effective and safe therapeutic agents. The present study is aimed at investigating the hepatoprotective potential of Seriphidium kurramense methanolic extract (SKM) against carbon tetrachloride- (CCl4-) induced hepatotoxicity in rats. S. kurramense is one of the most imperative plants for its various pharmacological activities. Therefore, this study was aimed at evaluating the hepatoprotective potential against CCl4-induced liver toxicity. The serum samples were analyzed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) together with the oxidative stress mediator levels as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), reduced glutathione (GSH), and superoxide dismutase (SOD) as well as peroxidation and H2O2 activity. CCl4 administration resulted in an elevated free radical generation, altered liver marker (AST and ALT) enzymes, reduced antioxidant enzyme, and increased DNA damage. Methanolic extract of S. kurramense decreased CCl4-induced hepatotoxicity by increasing the antioxidant status and reducing H2O2 and nitrate content generation as well as reducing DNA damage. Additionally, SKM reversed the morphological alterations induced by CCl4 in the SKM-treated groups. These results demonstrated that SKM displayed hepatoprotective activity against CCl4-induced hepatic damage in experimental rats.

An Insight into Phytochemical, Pharmacological, and Nutritional Properties of Arbutus unedo L. from Morocco.

Arbutus unedo L. (Ericaceae) is an evergreen shrub widely distributed in the Mediterranean region, particularly through the Moroccan forests. It is an important medicinal plant of great scientific interest due to its nutritional, pharmacological, and chemical properties. The objective of this review is to provide insights into traditional medicinal uses and phytochemical and pharmacological properties of A. unedo from Morocco. In Morocco, the plant has been used as a traditional medicine to treat several pathological conditions. Many phytochemical compounds have been reported in the plant, of which vitamins, carotenoids, flavonoids, polyphenols, tannins, and their derivatives are the most prevalent. Leaves and fruits of A. unedo contain the most significant number of phytochemicals among the species. Furthermore, researchers have demonstrated that A. unedo exhibited antioxidant, anticancer, antibacterial, antidiabetic, antiaggregant, and antihypertensive activities due to the presence of many biochemical compounds with health-promoting properties. According to different toxicity tests, the use of A. unedo is devoid of any significant side effects and/or toxicity. Despite its nutraceutical and health-promoting properties, Moroccan A. unedo remains underexploited mainly, and most of its traditional uses have not yet undergone scientific evidence-based research; therefore, improved knowledge about the potential value of the plant would allow understanding of its biological activity based on its phytochemical compounds that may contribute to the species preservation and valorization.

Tobacco Smoking and Liver Cancer Risk: Potential Avenues for Carcinogenesis.

Smoking a cigarette generates over 4000 chemicals that have a deleterious impact on each part of the human body. It produces three main severe effects on the liver organ: oncogenic, immunological, and indirect or direct toxic effects. It results in the production of cytotoxic substances, which raises fibrosis and necro-inflammation. Additionally, it also directs the production of pro-inflammatory cytokines tumour necrosis factor alfa (TNF-α) and interleukins (IL-1ß, IL-6) that will be responsible for the chronic liver injury. Furthermore, it gives rise to secondary polycythemia and successively raises the turnover and mass of red cells, which might be a common factor responsible for the development of oxidative stress in the liver due to iron overload. It also produces chemicals that are having oncogenic properties and raises the risk of liver cancer especially in sufferers of chronic hepatitis C. Smoking modulates both humoral and cell-mediated responses by restricting the proliferation of lymphocytes and inducing their apoptosis and ultimately decreasing the surveillance of cancer cells. Moreover, it has been determined that heavy smoking impacts the response of hepatitis C patients to interferon (IFN) therapy through different mechanisms, which can be improved by phlebotomy. Efforts are being made in different nations in decreasing the prevalence of smoking to improve premature death and ill effects of their nation's individuals.

Roles of Therapeutic Bioactive Compounds in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is due to poor prognosis and lack of availability of effective treatment. Novel therapeutic strategies will be the fine tuning of intracellular ROS signaling to effectively deprive cells of ROS-induced tumor-promoting events. This review discusses the generation of ROS, the major signaling their modulation in therapeutics. We explore some of the major pathways involved in HCC, which include the VEGF, MAPK/ERK, mTOR, FGF, and Ser/Thr kinase pathways. In this review, we study cornerstone on natural bioactive compounds with their effect on hepatocarcinomas. Furthermore, we focus on oxidative stress and FDA-approved signaling pathway inhibitors, along with chemotherapy and radiotherapy enhancers which with early evidence of success. While more in vivo testing is required to confirm the findings presented here, our findings will aid future nonclinical, preclinical, and clinical studies with these compounds, as well as inspire medicinal chemistry scientists to conduct appropriate research on this promising natural compound and their derivatives.

Notch Signaling and MicroRNA: The Dynamic Duo Steering Between Neurogenesis and Glioblastomas.

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.

Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy.

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent.

Paving Luteolin Therapeutic Potentialities and Agro-Food-Pharma Applications: Emphasis on In Vivo Pharmacological Effects and Bioavailability Traits.

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.

Therapeutic Potential of Isoflavones with an Emphasis on Daidzein.

Daidzein is a phytoestrogen isoflavone found in soybeans and other legumes. The chemical composition of daidzein is analogous to mammalian estrogens, and it could be useful with a dual-directional purpose by substituting/hindering with estrogen and estrogen receptor (ER) complex. Hence, daidzein puts forth shielding effects against a great number of diseases, especially those associated with the control of estrogen, such as breast cancer, diabetes, osteoporosis, and cardiovascular disease. However, daidzein also has other ER-independent biological activities, such as oxidative damage reduction acting as an antioxidant, immune regulator as an anti-inflammatory agent, and apoptosis regulation, directly linked to its potential anticancer effects. In this sense, the present review is aimed at providing a deepen analysis of daidzein pharmacodynamics and its implications in human health, from its best-known effects alleviating postmenopausal symptoms to its potential anticancer and antiaging properties.

Ethnomedicinal Use, Phytochemistry, and Pharmacology of Xylocarpus granatum J. Koenig.

The mangrove plants are the potential sources of foods and remedies for people living in the forests and nearby communities. Xylocarpus granatum J. Koenig is traditionally used to treat various diseases including diarrhea, cholera, dysentery, fever, malaria, and viral infections, among others. To summarize critically the taxonomy, ethnomedicinal, phytochemistry, and pharmacological activities of X. granatum, information was collected from different databases. An up-to-date search (till June 2020) was carried out with the help of various scientific web resources from databases such as PubMed, Science Direct, Google Scholar, and various patent offices (e.g., WIPO, CIPO, and USPTO) using the keywords "Xylocarpus granatum" and then paired with ethnomedicinal use and phytochemical, phytochemistry, and pharmacological activity (in vitro, ex vivo, and in vivo studies). Findings revealed that seeds, fruits, stem bark, leaf, and twigs of X. granatum exhibited a wide range of key phytochemicals including limonoids, phragmalin, limonoid-based alkaloids, mexicanolides, protolimonoids, flavonols, and lactones. The plant possessed potent antioxidant, anticancer, antidiabetic, antimicrobial, antimalarial, antifeedant, and neuroprotective activities. No clinical studies have been reported in the databases. Ethnomedicinal assessment indicated the application of X. granatum in various fields of medical science specially to treat various human ailments, and this was attributed to the presence of enormous alkaloids as confirmed by pharmacological studies. However, to understand the mechanism of action in-depth studies are required. In view of these findings, more research is necessary to explore and characterize the chemical compounds and toxicological aspects of this medicinal mangrove plant. Overall, it can be stated that X. granatum may be one of the hopeful medicinal herbs for the treatment of various diseases in human beings.

Lasia spinosa Chemical Composition and Therapeutic Potential: A Literature-Based Review.

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: "Lasia spinosa," then combined with "ethnopharmacological use," "phytochemistry," and "pharmacological activity." This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans.

Investigation of anti-proliferative and antioxidative effects of some bis (α-amino) phosphinic acid derivatives.

Aminophosphinic acids which are organophosphorus compounds widely investigated for potential production of antibacterial, antitumor and antiviral materials. In vitro antioxidant, cytotoxic and antimicrobial activities of synthesized novel compounds of 8 different bis(ß-amino alkyl)phosphinic acids (4a-h) were investigated on MCF-7 breast adenocarcinoma cell and human umbilical vein endothelial cell (HUVEC) cultures. Malondialdehyde (MDA) levels were evaluated as an indication of lipid peroxidation in cell cultures for antioxidant capacities. In vitro antioxidant activities in cell cultures were determined by evaluating totals of antioxidant, oxidant, thiol levels and activities of paraoxanase, aryl esterase. It was found that 4c compound reduced MDA level significantly while 4a and 4g compounds increased MDA levels significantly compared to control. 4c compound was found most effective in reducing MDA levels by neutralizing reactive oxygen species to prevent cell damage while compounds 4c, 4f and 4h were found presenting adequate activity with other antioxidants. In vitro anti-proliferation was evaluated on MCF-7 and HUVEC cells using XTT to investigate anti-cancer potentials as therapeutics. Compounds 4c, 4e and 4f were exhibited better compared to others. Most compounds were found cytotoxic to both MCF-7 and HUVECs. Antimicrobial and antifungal activities were investigated by disc diffusion and compared to MICs of Gentamycin and Nystatin.