Mechanochemical Solvent-Free One-Pot Synthesis of Poly-Functionalized 5-(Arylselanyl)-1H-1,2,3-triazoles Through a Copper(I)-Catalyzed Click Reaction.

A mechanochemistry-driven practical and efficient synthetic protocol for accessing diverse series of biologically relevant poly-functionalized 5-(arylselanyl)-1H-1,2,3-triazoles through copper(I)-catalyzed click reaction between aryl/heteroaryl acetylenes, diaryl diselenides, benzyl bromides, and sodium azide has been accomplished under high-speed ball-milling. Advantages of this method include operational simplicity, avoidance of using solvent and external heating, one-pot synthesis, short reaction time in minutes, good to excellent yields, broad substrate scope, and gram-scale applications. Furthermore, synthesized organoselenium compounds were synthetically diversified to biologically promising selenones.

Electrochemical Regioselective C(sp2)-H Selenylation and Sulfenylation of Substituted 2-Amino-1,4-naphthoquinones.

A straightforward and efficient electrochemical method for regioselective C(sp2)-H selenylation and sulfenylation of substituted 2-amino-1,4-naphthoquinones has been unearthed. This oxidative cross-coupling reaction avoids using transition metal catalysts, oxidants, and high temperatures. The other notable advantages of this protocol are the tolerance of diverse functional groups, mild reaction conditions at ambient temperature, energy efficiency, good to excellent yields, short reaction times (in minutes), gram-scale applicability, and eco-friendliness.

Catalyst- and Additive-Free C(sp3)-H Functionalization of (Thio)barbituric Acids via C-5 Dehydrogenative Aza-Coupling Under Ambient Conditions.

A one-pot room-temperature-based three-component reaction strategy has been accomplished to access a new series of bio-relevant barbituric/2-thiobarbituric acid hydrazones from the reaction between barbituric/2-thiobarbituric acids, primary aromatic amines, and tert-butyl nitrite in an acetonitrile solvent, without the aid of any catalysts/additives. The ambient reaction conditions can efficiently implement the C(sp3)-H functionalization of barbituric/2-thiobarbituric acids via C-5 dehydrogenative aza-coupling. The process does not require column chromatographic purification; pure products are obtained by simple filtration of the resulting reaction mixture, followed by washing the crude residue with distilled water. The catalyst-free ambient reaction conditions, operational simplicity, broad substrate scope and tolerance for various functional groups, no need for chromatographic purification, good to excellent yields of products within reasonable reaction times in minutes, clean reaction profile, and gram-scale synthetic applicability make this procedure attractive, green, and cost-effective.

An Updated Review on Biologically Promising Natural Oxepines.

Benzo-oxepines and dibenzo-oxepines, a unique class of naturally occurring secondary metabolites, are distributed mainly in plants and fungi and have received much attention from phytochemists and biologists based on their fascinating structural features and health-promoting functions. This review summarizes 100 oxepine derivatives comprising three categories: benzo-oxepine, dibenzo-oxepine, and pyrano-oxepine. Studies on various structural features and pharmacological activities of oxepine derivatives promote further in-depth research on these potent natural products. This review portrays the natural occurrence, bioactivity and biosynthesis of oxepines reported from 1984 to 2021.

Screening of Synthetic Heterocyclic Compounds as Antiplatelet Drugs.

BACKGROUND: Antiplatelet drugs represent the keystone in the treatment and prevention of diseases of ischemic origin, including coronary artery disease. The current palette of drugs represents efficient modalities in most cases, but their effect can be limited in certain situations or associated with specific side effects. In this study, representatives of compounds selected from series having scaffolds with known or potential antiplatelet activity were tested. These compounds were previously synthetized by us, but their biological effects have not yet been reported. OBJECTIVE: The aim of this study was to examine the antiplatelet and anticoagulation properties of selected compounds and determine their mechanism of action. METHODS: Antiplatelet activity of compounds and their mechanisms of action were evaluated using human blood by impedance aggregometry and various aggregation inducers and inhibitors and compared to appropriate standards. Cytotoxicity was tested using breast adenocarcinoma cell cultures and potential anticoagulation activity was also determined. RESULTS: In total, four of 34 compounds tested were equally or more active than the standard antiplatelet drug Acetylsalicylic Acid (ASA). In contrast to ASA, all 4 active compounds decreased platelet aggregation triggered not only by collagen, but also partly by ADP. The major mechanism of action is based on antagonism at thromboxane receptors. In higher concentrations, inhibition of thromboxane synthase was also noted. In contrast to ASA, the tested compounds did not block cyclooxygenase- 1. CONCLUSION: The most active compound, 2-amino-4-(1H-indol-3-yl)-6-nitro-4H-chromene-3- carbonitrile (2-N), which is 4-5x times more potent than ASA, is a promising compound for the development of novel antiplatelet drugs.

Visible Light-Driven and Singlet Oxygen-Mediated Photochemical Cross-Dehydrogenative C3-H Sulfenylation of 4-Hydroxycoumarins with Thiols Using Rose Bengal as a Photosensitizer.

A visible light (white light-emitting diode/direct sunlight)-driven photochemical synthesis of a new series of biologically interesting 3-(alkyl/benzylthio)-4-hydroxy-2H-chromen-2-ones has been achieved through a cross-dehydrogenative C3-H sulfenylation of 4-hydroxycoumarins with thiols at ambient temperature in the presence of rose bengal in acetonitrile under an oxygen atmosphere. The notable features of this newly developed method are mild reaction conditions, energy efficiency, metal-free synthesis, good to excellent yields, use of low-cost materials, and eco-friendliness.

Visible Light-Induced and Singlet Oxygen-Mediated Photochemical Conversion of 4-Hydroxy-α-benzopyrones to 2-Hydroxy-3-oxo-2,3-dihydrobenzofuran-2-carboxamides/carboxylates Using Rose Bengal as a Photosensitizer.

Development of a visible light-induced and singlet oxygen-mediated green protocol has been accomplished for the first time for the photochemical transformation of 4-hydroxy-α-benzopyrones to a new series of biorelevant 2-hydroxy-3-oxo-2,3-dihydrobenzofuran-2-carboxamides and 2-hydroxy-3-oxo-2,3-dihydrobenzofuran-2-carboxylates using rose bengal as a triplet photosensitizer at ambient temperature. Metal-free one-pot synthesis, broader substrate scope, good-to-excellent yields, use of cost-effective and eco-friendly starting materials and photosensitizer, and energy efficiency are the salient features of this newly developed method.

Series of Functionalized 5-(2-Arylimidazo[1,2-a]pyridin-3-yl)pyrimidine-2,4(1H,3H)-diones: A Water-Mediated Three-Component Catalyst-Free Protocol Revisited.

A water-mediated and catalyst-free practical method for the synthesis of a new series of pharmaceutically interesting functionalized 5-(2-arylimidazo[1,2-a]pyridin-3-yl)pyrimidine-2,4(1H,3H)-diones has been accomplished based on a one-pot multicomponent reaction between arylglyoxal monohydrates, 2-aminopyridines/2-aminopyrimidine, and barbituric/N,N-dimethylbarbituric acids under reflux conditions. The salient features of this protocol are avoidance of any additive/catalyst and toxic organic solvents, use of water as reaction medium, clean reaction profiles, operational simplicity, ease of product isolation/purification without the aid of tedious column chromatography, good to excellent yields, and high atom-economy and low E-factor.

Amelioration of oxidative DNA damage in mouse peritoneal macrophages by Hippophae salicifolia due to its proton (H(+)) donation capability: Ex vivo and in vivo studies.

INTRODUCTION: The present study evaluates the antioxidant effect of methanol extract of Hippophae salicifolia (MEHS) bark with special emphasis on its role on oxidative DNA damage in mouse peritoneal macrophages. MATERIAL AND METHODS: In vitro antioxidant activity was estimated by standard antioxidant assays whereas the antioxidant activity concluded the H(+) donating capacity. Mouse erythrocytes' hemolysis and peritoneal macrophages' DNA damage were determined spectrophotometrically. In vivo antioxidant activity of MEHS was determined in carbon tetrachloride-induced mice by studying its effect on superoxide anion production in macrophages cells, superoxide dismutase in the cell lysate, DNA damage, lipid peroxidation, and reduces glutathione. RESULTS: The extract showed good in vitro antioxidant activities whereas the inhibitory concentrations values ranged from 5.80 to 106.5 µg/ml. MEHS significantly (P < 0.05) attenuated the oxidative DNA damage. It also attenuated the oxidative conversion of hemoglobin to methemoglobin and elevation of enzymatic and nonenzymatic antioxidant in cells. CONCLUSION: The result indicates MEHS has good in vitro-in vivo antioxidant property as well as the protective effect on DNA and red blood cell may be due to its H(+) donating property.

Regulation of apoptosis through bcl-2/bax proteins expression and DNA damage by Zanthoxylum alatum.

CONTEXT: Many of the major chemotherapeutic agents are secondary metabolites found in nature. Zanthoxylum alatum Roxb. (Rutaceae) is traditionally used in the treatment of various diseases. OBJECTIVE: The present study evaluates the apoptotic activity of methanol extract of Z. alatum (MEZA) on Ehrlich ascites tumor (EAT) in Swiss albino mice. MATERIALS AND METHODS: The presence of flavonoids in MEZA was standardized by HPLC. The in vitro cytotoxicity of MEZA was measured by the MTT assay. The in vivo antitumor activity of MEZA (100 and 200 mg/kg b.w., i.p. for 9 days) was also evaluated. On the 10th day, EAT tumor volume, cell viability, and hematological parameters were assayed. Apoptotic morphology was determined by acredine orange/ethedium bromide using fluorescence microscopy. Apoptosis percentage was measured by flow cytometric analysis using annexine-V-FITC. Also, DNA damage and bcl-2/bax were estimated by UV-method and western blot, respectively. RESULTS AND DISCUSSION: HPLC analysis revealed presence of three flavonoids, rutin, myricetin, and quercetin. MEZA showed satisfactory cytotoxicity in MTT assay (IC50 = 111.50 µg/ml). The extract significantly (p < 0.01) changed the tumor volume, viable, non-viable cell count, and hematological parameters towards the normal. Apoptotic activity of MEZA was confirmed by acridine orange/ethidium bromide staining, annexin-V-FITC staining, DNA fragmentation, and Bcl-2/Bax ratio. CONCLUSION: The study showed that MEZA has antitumor activity which may be due to the presence of flavonoids in the extract.

Antitumor Potential of Thevetia peruviana on Ehrlich's Ascites Carcinoma-Bearing Mice.

Methanol extracts of Thevetia peruviana (METP) (Apocynaceae) fruit showed antitumor activity against Ehrlich's ascites carcinoma (EAC) cell line in Swiss albino mice. The METP-treated group's tumor volume, tumor weight, and viable cell count were decreased compared to the EAC control group. Tumor volumes were 3.62±0.12 ml, 2.88±0.23 ml, and 1.34±0.17 ml for the EAC control group and the METP-treated groups (50 mg/kg and 100 mg/kg body weight), respectively. Nonviable cell counts were 4.44%±0.42%, 18.57%±3.07%, and 68.12%±5.32% in the EAC control group and the METP-treated groups (50 mg/kg and 100 mg/kg body weight), respectively. METP-treated EAC cell-bearing mice had an increased life span (48.69% and 83.78%) compared to the EAC control group. Hematological and serum biochemical profiles were restored to normal levels in METP-treated mice compared to the EAC control group. METP significantly (P<0.001) decreased lipid peroxidation and recovered reduced glutathione, superoxide dismutase, and catalase toward normal levels compared to the EAC control group. In summary, METP exhibited remarkable antitumor activity in Swiss albino mice, which is plausibly attributable to its augmentation of endogenous antioxidant mechanisms.

Antitumor activity and antioxidant status of Streblus asper bark against Dalton's ascitic lymphoma in mice.

Streblus asper Lour (Moraceae), commonly known as Siamee Rough Brush in English is widely distributed in subtropical Asia and traditionally used for several medicinal purposes. In the present study, the ethyl acetate fraction of the methanol extract from Streblus asper bark (EASA) was evaluated for antitumor effect against Dalton's ascitic lymphoma (DAL) in Swiss albino mice. Twenty-four hours after intraperitoneal inoculation of DAL cells in mice, EASA was administered intraperitoneally at 200 and 400 mg/kg body weight for 9 consecutive days. On the 10th day, half of the mice were sacrificed to determine the tumor growth parameters, and the rest were kept alive for survival assessment. Hematological, serum biochemical and tissue (liver, kidney) antioxidant profiles were also determined. EASA exhibited significant and dose dependent decrease in tumor growth parameters and increased survival of DAL bearing animals. EASA significantly and dose-dependently normalized the altered hematological, serum biochemical and tissue antioxidant parameters as compared with the DAL control mice. From the present study it may be concluded that S. asper bark possesses remarkable antitumor efficacy mediated by amelioration of oxidative stress by multiple mechanisms.

Antitumor activity and antioxidant property of Curcuma caesia against Ehrlich's ascites carcinoma bearing mice.

CONTEXT: Curcuma caesia Roxb. (Zingiberaceae), commonly known as "Kala Haldi" in Bengali, has been traditionally used for the treatment of cancer, bruises, inflammation and as an aphrodisiac. OBJECTIVE: To evaluate the antitumor activity and antioxidant status of the methanol extract of Curcuma caesia (MECC) rhizomes on Ehrlich's ascites carcinoma (EAC)-treated mice. MATERIALS AND METHODS: In vitro cytotoxicity assay of MECC was evaluated by using Trypan blue method. Determination of in vivo antitumor activity was performed after 24 h of EAC cells (2 × 10(6) cells/mouse) inoculation; MECC (50 and 100 mg/kg i.p.) was administered daily for nine consecutive days. On day 10, half of the mice were sacrificed and the rest were kept alive for assessment of increase in lifespan. Antitumor effect of MECC was assessed by the study of tumor volume, tumor weight, viable and non-viable cell count, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes. RESULTS: MECC showed direct cytotoxicity (IC50 90.70 ± 8.37 µg/mL) on EAC cell line. MECC exhibited significant (p < 0.01) decrease in tumor volume, tumor weight, viable cell count and percentage increased the lifespan (57.14 and 88.09%) of EAC-treated mice. Hematological profile, biochemical estimation, tissue antioxidant assay significantly (p < 0.01) reverted to normal level in MECC-treated mice. CONCLUSION: MECC possesses potent antitumor activity that may be due to its direct cytotoxic effect or antioxidant properties. Further research is in progress to find out the active principle(s) of MECC for its antitumor activity.

Antitumor activity and antioxidant role of Streblus asper bark against Ehrlich ascites carcinoma in Swiss albino mice.

The present study assessed the methanol extract of Streblus asper stem bark (MESA) for antitumor effect and antioxidant influence against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. Twenty four hours after intraperitonial inoculation of tumor (EAC) cells in mice, MESA was administered at 200 and 400 mg/kg body weight daily for 9 consecutive days. On the 10 th day, half of the mice were sacrificed for estimation of tumor parameters, haematological, liver and kidney antioxidant parameters; and the rest were kept alive for assessment of survival. MESA exhibited dose dependent and significant (p < 0.01) decrease in tumor proliferation and extended the life span of EAC bearing mice. Hematological profiles were significantly (p < 0.01) restored near to normal in MESA treated mice as compared to EAC control. MESA treatment significantly (p < 0.01) modulated the hepatic and renal antioxidant parameters as compared to EAC control. The present study demonstrated that S. asper bark possessed promising antitumor efficacy in mice, plausibly mediated by amelioration of oxidative stress by multiple mechanisms.

Antitumor potential of Castanopsis indica (Roxb. ex Lindl.) A. DC. leaf extract against Ehrlich's ascites carcinoma cell.

Methanol extract of C. indica (MECI) leaves showed direct cytotoxicity on Ehrlich ascites carcinoma (EAC) cell in a dose dependant manner and there was significant decrease in the tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. Hematological profile and biochemical estimations were significantly restored to normal levels in MECI treated as compared to EAC control mice. MECI treatment significantly modulated the tissue antioxidant assay parameters as compared to the EAC control mice. The results revealed that MECI possesses significant dose dependent antitumor potential which may be due to its cytotoxicity and antioxidant properties.

Evaluation of antitumor activity and in vivo antioxidant status of Anthocephalus cadamba on Ehrlich ascites carcinoma treated mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Anthocephalus cadamba (Roxb.) Miq. (Family: Rubiaceae) is commonly known as "Kadamba" in Sanskrit and Hindi in India. Various parts of this plant have been used as a folk medicine for the treatment of tumor, wound healing, inflammation and as a hypoglycemic agent. AIM OF STUDY: The purpose of this investigation was to evaluate the antitumor activity and antioxidant status of defatted methanol extract of A. cadamba (MEAC) on Ehrlich ascites carcinoma (EAC) treated mice. MATERIALS AND METHODS: In vitro cytotoxicity assay has been evaluated by using the trypan blue method. The determination of in vivo antitumor activity was performed by using different EAC cells (2 × 10(6) cells, i.p.) inoculated mice groups (n=12). The groups were treated for 9 consecutive days with MEAC at the doses of 200 and 400 mg/kg b.w. respectively. After 24h of last dose and 18 h of fasting, half of the mice were sacrificed and the rest were kept alive for assessment of increase in life span. The antitumor potential of MEAC was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes. RESULTS: MEAC showed direct cytotoxicity on EAC cell line in a dose dependant manner. MEAC exhibited significant (P<0.01) decrease in the tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. The hematological profile, biochemical estimations and tissue antioxidant assay were reverted to normal level in MEAC treated mice. CONCLUSION: Experimental results revealed that MEAC possesses potent antitumor and antioxidant properties. Further research is going on to find out the active principle(s) of MEAC for better understanding of mechanism of its antitumor and antioxidant activity.