THERAPEUTIC POTENTIAL AND IN VITRO ANTHELMINTIC ACTIVITY OF RIDGE GOURD FRUIT

Objective: The objective of the study was to evaluate the therapeutic potential and in vitro anthelmintic activity of ridge gourd fruit (Luffa acutangula) against Indian earthworms. Methods: For anthelmintic activity against Indian earthworms (Pheretima posthuma, Ascaridia galli, and Raillietina spiralis), various different extracts concentration of L. acutangula fruit have been taken. Five concentrations as 10, 20, 30, 40, and 50 mg/ml of various extracts were tested and results were expressed in terms of time for paralysis and time for the death of worms. Albendazole (20 mg/ml) was used as reference standard and water (0.5%) as a control group. Results: Preliminary phytochemical screening of the different extracts of ridge gourd fruit was shown to produce anthelmintic activities. In the present study, it was observed that all the extracts of ridge gourd fruit have exhibited a positive response to a certain degree of anthelmintic activity. Ethyl acetate extract exhibited more potent activity at the lower concentration of 10 mg/mL against A. galli (Roundworm). The anthelmintic activity of L. acutangula fruit extract has, therefore, been demonstrated

The critical role of novel benzophenone analogs on tumor growth inhibition targeting angiogenesis and apoptosis

In modern biology, one of the major topics of importance is progress in anti-cancer drugs with specific targets. The angiopreventive and in vitro tumor inhibition activities of novel synthetic benzophenone analogs have been investigated intensively and explored in a very systematic way. Novel benzophenone analogs (9a–d and 10a–d) substituted with methyl, chloro and fluoro groups at different positions on an identical chemical backbone and incorporating variations in the number of substituents have been synthesized in a multistep process and characterized. In this study, we further evaluate the newly synthesized compounds for their cytotoxic and anti-proliferative effects against A549, HeLa and MCF-7 cells. The potent lead compound was further assessed for anti-angiogenic effects. Through the structure–activity relationship, we found that an increase in the number of methyl, chloro and fluoro groups in a benzophenone ring on compound 9d resulted in higher potency compared to other compounds. Tumor inhibition was notably promoted, and this was reflected in effects on neovessel formation in in vivo systems, such as the CAM. Compound 9d interacts with rVEGF through hydrogen bonds in silico, thereby down-regulating the expression of VEGF in angiogenesis. From our investigation, it is suggested on the basis of clonogenesis and cell migration assays that compound 9d has the potency to exhibit prolonged activity against cancer progression, through cell cycle arrest at the G2/M phase. In addition, compound 9d inhibits A549 cells through caspase-activated DNase-mediated apoptosis

IN VITRO EVALUATION OF HYPOLIPIDEMIC EFFECT OF EXTRACTS OF MEDICINAL DRACAENA CINNABARI BALF. F. RESIN: In vitro evaluation of hypolipidemic effect

Objective: The objective of the study was to in vitro evaluate of hypolipidemic effect of extracts of medicinal Dracaena cinnabari Balf. f. resin. Methods: About 800 g of dry powder of the resin of dracaena cinnabar was taken in a Soxhlet apparatus and subjected for sequential extraction of solvents from non-polar to polar end (hexane, benzene, diethyl ether, dichloromethane, chloroform, ethyl acetate, acetone, ethanol, methanol, and water); the extract samples were kept at 4°C for further assays. All the extracts were subjected to glucose uptake assay. Results: The ethanol extract showed significant (p<0.05) hypolipidemic effect by decreasing the activity of enzyme such as significant reduction in the pancreatic lipase enzyme, malic dehydrogenase enzyme, and glucose-6-phosphate dehydrogenase enzyme with IC50~13, ~13, and ~14, respectively. This results were similar to the standard drug atorvastatin with IC50~12, ~16, and ~17, respectively. Ethanol extract exhibited significant atherogenic index and percentage protection against hyperlipidemia. The potential biological activity of ethanol extract may be attributed to the highest polarity which needs further investigation

Effect of o-difluoro and p-methyl substituents on the structure, optical properties and anti-inflammatory activity of phenoxy thiazole acetamide derivatives: Theoretical and experimental studies

Thiazole derivatives (6a and 6b) have been synthesized and characterised by H-1 - C-13 NMR, as well as LC-MS spectra. The three-dimensional structures have been confirmed by single crystal X-ray diffraction method. 6a and 6b compounds have been crystallized in the Triclinic and the Orthorhombic systems with P-1 and Pbca space groups, respectively. Supramolecular structures revealed the stability of molecules with different intermolecular interactions and different crystal packing environment. Theoretical study by Density functional theory (DFT) with B3LYP functional based on highest basis set 6-311++G(d,p) was employed to calculate the geometry and compared to the experimental data. The electronic structures and intramolecular charge transfers have been investigated by using natural population and natural bond orbital analysis (HBO). Further, DFT studies were performed to assess the frontier molecular orbitals (FMOs), energy gap, softness, hardness, and others chemical reactivity. Hirshfeld surface was investigated to distinguish the different interatomic contacts and understand the crystal packing of molecules with aid of energy frameworks through different intermolecular interaction energies based on the anisotropy of the topology. Nonlinear optical property (NLO) of the synthesized molecules were predicted by (DFT) and examined experimentally by using second harmonic generation (SHG) and revealed the importance of high NLO based on the nature of substituents and conformation. Thiazole derivatives were assessed for anti-inflammation activity by in silico molecular docking studies against COX-1 and COX-2 protein receptors revealed prominent interactions with active site and further molecular dynamics confirms the stability of the protein-ligand model. In vitro assay against cyclooxygenase (COX) enzyme gave IC50 values of 6a and 6b molecules with ortho-difluoro and para-methyl positions on benzoyl group, showed better inhibitor for COX-1 and COX-2, respectively. (C) 2019 Elsevier B.V. All rights reserved

Synthesis, molecular docking, and apoptogenic efficacy of novel N-heterocycle analogs to target B-cell lymphoma 2/X-linked inhibitors of apoptosis proteins to regress melanoma

The novel series of piperidine conjugated benzophenone analogs with amide link 11a–l were synthesized in a multistep process. The structures of these compounds were confirmed by IR, 1H, 13C, NMR, and mass spectra and also by elemental analyses. The newly synthesized molecules were screened for selectivity against cancers of different origin through cell based assay system using B16F10, A375, A549, HepG2, ACHN, and MCF7 cells. The results postulated that compound 11f with two bromo groups at the para position in rings A and E and two methyl groups at ortho position in rings B and D evokes target specific action against melanoma highlighting the importance of substituted groups. Down the line studies further inferred compound 11f evokes the apoptotic cellular event leading to cell death. Investigation of eventual mechanism revealed that compound 11f turned out to be a dual inhibitor of B-cell lymphoma-2 and X-linked inhibitors of apoptosis causing the up regulation of Bax and Bad. Further, the antiproliferative effects were mimicked in murine melanoma with similar mechanisms. Molecular docking experiments further confirmed that compound 11f possessed a superior affinity for of B-cell lymphoma-2 and X-linked inhibitors of apoptosis through strong hydrogen bonds. The study implies the identification of compound 11f with selective target against melanoma by inducing apoptogenic effect, which could be the future hope for the treatment of skin cancer

Synthesis, spectroscopic and X-ray crystallographic analysis of N-(2-(2-(4-chlorophenoxy)acetamido)phenyl)-1H-indole-2-carboxamide

Medicinal chemistry of indole analogs constitutes important therapeutic agents with anti-oxidant, anti-HIV and anti-cancer activities. Indole nucleus is frequently found in synthetic and natural products, pharmaceuticals, functional materials, agrochemicals, etc. The title compound, N-(2-(2-(4-chlorophenoxy)acetamido)phenyl)-1H-indole-2-carboxamide (5), has been synthesized in good yield by stirring the compound N-(2-aminophenyl)-2-(4-chlorophenoxy)acetamide (3) with 1H-indole-2-carboxylic acid (4), in dry dichloromethane followed by the addition of 2,6-lutidine, and o-(benzotriazol-1-yl)-N,N,N',N'-tetramethyl uraniumtetrafluoroborate in cooled condition. Compound 5 was synthesized and characterized by the conventional spectroscopic techniques (1H NMR, 13C NMR and LC-MS) and the three-dimensional structure was elucidated by using single crystal X-ray diffraction methods. It crystallizes in the monoclinic crystal system with space group P21/c. The structure was solved by direct methods and refined by full matrix least square procedure to a final R value of 0.043 for 2490 observed reflections. Three intra-molecular interactions of the type N-H···N and C-H···N were observed. The packing of molecules in the unit cell is governed by N-H···O and C-H···O intermolecular H-boned interactions which leads to the formation of infinite staking chain along [001] direction. In addition, two weak C-H···π interactions also contribute to molecular packing

Design-based synthesis, molecular docking analysis of an anti-inflammatory drug, and geometrical optimization and interaction energy studies of an indole acetamide derivative

The new indole acetamide, N-(2-(2-(4-Chlorophenoxy)acetamido)phenyl)-2-carboxamide-1H-indole (5) has been synthesized with good yield by stirring the compound N-(2-Aminophenyl)-2-(4-chlorophenoxy)acetamide (3) with 1H-indole-2-carboxylic acid (4), in dry dichloromethane (DCM) followed by the addition of lutidine, and N,N,N',N'-O-(Benzotriazole-1-yl)-tetramethyluronium tetrafluoroborate (TBTU) in cooled condition. The compound obtained was characterized by spectroscopic analyses (MS, FT-IR, H-1 NMR, C-13 NMR, UVevisible, and elemental). The anti-inflammatory activity was confirmed by in silico modeling study, which target the cyclooxygenase COX-1 and 2 domains. The three-dimensional structure was determined using single crystal X-ray diffraction studies. Geometry optimization of the compound was done using density functional theory calculations by employing B3LYP hybrid functional basis set. Vibrational analysis of the compound revealed that the optimized structure is not in an excited state. Frontier molecular orbitals Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) were analyzed to understand the electronic charge transfer within the molecule. To analyze the intermolecular interactions in the crystal, Hirshfeld surface analysis was carried out. Energy frameworks were constructed to investigate the stability of the compound. Atom in molecule (AIM) calculations were performed to validate the different intramolecular interactions. (C) 2019 Elsevier B.V. All rights reserved

Synthesis, crystal structure elucidation, Hirshfeld surface analysis, 3D energy frameworks and DFT studies of 2-(4-fluorophenoxy) acetic acid

The compound 2-(4-fluorophenoxy) acetic acid was synthesized by refluxing, 4-fluoro-phenol as a starting material with ethyl chloroacetate in acetone as solvent. The compound crystallizes in the monoclinic crystal system with the space group P21/c. Crystal data for C8H7FO3, a = 13.3087(17) Å, b = 4.9912(6) Å, c = 11.6018(15) Å, β = 104.171(4)°, V = 747.21(16) Å3, Z = 4, T = 293(2) K, μ(CuKα) = 1.142 mm-1, Dcalc = 1.512 g/cm3, 8759 reflections measured (13.72° ≤ 2Θ ≤ 130.62°), 1246 unique (Rint = 0.0528) which were used in all calculations. The final R1 was 0.0458 (>2sigma(I)) and wR2 was 0.1313 (all data). The structure was stabilized by C-H···O and C-H···Cg interactions. The intermolecular interactions in the crystal were studied using Hirshfeld surface analysis. 3D energy frameworks were computed to visualize the packing modes. DFT calculations were performed. The FMOs were studied to estimate the kinetic stability and reactivity of the molecule. The MEP surface was generated to investigate the charge distribution and chemical reactive sites in the molecule

Crystal packing analysis of 1-(3,4-dimethoxyphenyl)-3-(4-bromophenyl)prop-2-en-1-one exhibiting a putative halogen bond CBr⋯O

The title compound, 1-(3,4-dimethoxyphenyl)-3-(4-bromophenyl) prop-2-en-1-one (1DBr) was synthesized and characterized based on spectroscopic analysis (MS, FT-IR, Elemental analysis, UV–visible, 1H NMR and 13C NMR) and finally the three-dimensional structure is confirmed using single crystal X-ray diffraction studies. The molecule is almost planar and the C---H⋯O intramolecular hydrogen bond closes the ring S(5). In the crystal structure, the molecules are connected through intermolecular hydrogen bond C---H⋯O (R22(14) ring motif) and intermolecular interactions (C---H⋯π and C---O⋯π). Hirshfeld surfaces computational method was employed to quantify the inter-contacts (2D Fingerprint plots) and calculate enrichment ratio (E). The highest value of E is calculated for the contact Br⋯O (1.65) followed by C⋯C (1.02) and have high propensity for forming contacts in the crystal. This provides the basis for the existence of putative halogen bond of the type C--Br⋯O. In addition, the Energy-framework analysis was used to analyze and visualize the 3D-topology of the crystal packing. The dispersion energy framework is dominated over the electrostatic energy-frameworks. The thermogravimetric analysis (TGA) provided the thermal degradation of the 1DBr to be from 230 to 320 °C

The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases

Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton’s solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H- bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent