When a doctor is required to go to court, he does so with some amount of trepidation. The degree of trepidation increases in direct proportion as to whether he is required to be a witness or a defendant. The practice of medicine on the other hand requires the patient to have full confidence and open out his secrets to the doctor. If you hold back vital information, the diagnosis may be entirely different to the disease that you have. Lawyers who enter hospitals may also do so with some trepidation, maybe even more so than doctors who enter courts, as their lives are at stake. There is a perception that medico-legal matters are on the rise. We may put forward a few reasons for this: 1. A better educated and increasingly assertive public with greater awareness of the medical and legal systems; 2. Rising expectations of medical results; 3. Commercialization of medical care with erosion of the doctor-patient trust relationship. This paper will discuss the reasons for and the ways to address medical errors as well as explore the reasons for defensive medicine. The argument is put forward that public education programs on the risks inherent in some of the new advances in treatment modalities and surgery and professional education programs on the need for obtaining the patient's informed consent to such treatment is needed. Public advocacy programs to demonstrate the problems in medicine and the delivery of health care resulting from strict cost containment limitations should be carried out. There is also the need to enhance the level and quality of medical education for all physicians, including improved clinical training experiences. Doctors' must manage their clinical affairs in a professional manner without being dictated to by the legal system. However, it would be wise to take note of the views expressed by learned counsel and judges in their courts. The middle road is always the best and we must never be extreme in our viewpoints. We must always remember the patient is why we are here and the patient must never suffer in the process while we formulate our responses to the medico-legal challenges that lie ahead.
The purpose of this research is to investigate the influence of supervisory relationship on supervision satisfaction among trainee counselors. The Supervisory Relationship Questionnaire (SRQ) is to measure the supervisory relationship and Supervisory Satisfaction Questionnaire (SSQ) is used to measure supervision satisfaction. The finding shows that supervisory relationship and its subscales (Safe Base, Structure, Commitment, Reflective Education, Role Model and Formative Feedback) have a positively significant relationship with supervision satisfaction among trainee counselors (safe base: r = 0.73, p < 0.05, structure: r = 0.65, p < 0.05, commitment: r = 0.69, p < .05, reflective education: r = 0.70, p < 0.05, role model: r = 0.51, p < 0.05, formative feedback: r = 0.71, p < 0.05 and supervisory relationship: r = 0.79, p < 0.05). The findings of this research also found that supervisory relationship, safe base and role model variables have significant influence on supervision satisfaction among trainee counselors with F (1, 98) = 169.59, p < 0.05, Adjusted R2 = 0.63 for supervisory relationship variable, F (3, 96) = 68.68, p < 0.05, Adjusted R2 = 67 for safe base variable and F (2, 97) = 96.47, p < 0.05, Adjusted R2 = 0.65 for role model variable. Supervisory relationship variable has the greatest influence (β = .79) while role model variable has the least influence (β = - 0.28) on supervision satisfaction. As for the theoretical implication, the finding of this research has proven Marina Palomo’s theoretical framework in ‘Bi-directional Model of the Supervisory Relationship’. Meanwhile in practical implication, this research has raised awareness on the importance of supervisory relationship on supervision satisfaction in counseling supervision.
Bisindolylmethane and its derivatives are pharmacologically active and applicable in the field of pharmaceutical chemistry. Bisindolylmethanes have a variety of biological activities such as antihyperglycemic, antiinflammatory, antibacterial, anticancer, and antileishmanial activities, including enzyme inhibition activity. They play a crucial role in many diseases especially anticancer activity. Modifying their structure had proven to be useful in the search of new therapeutic agents. Extensive research carried out on bisindolylmethane and its derivatives shows that they are pharmacologically significant. The present review focuses on the pharmacological profile of bisindolylmethane derivatives. This review includes the current literature with an update of research findings as well as the perspectives that they hold for future research.
Inhibition of Thymidine phosphorylase (TP) is continuously studied for the design and development of new drugs for the treatment of neoplastic diseases. As a part of our effort to identify TP inhibitors, we performed a structure-based virtual screening (SBVS) of our compound collection. Based on the insights gained from structures of virtual screening hits, a scaffold was designed using 1,3,4-oxadiazole as the basic structural feature and SAR studies were carried out for the optimization of this scaffold. Twenty-five novel bis-indole linked 1,3,4-oxadiazoles (7-31) were designed, synthesized and tested in vitro against E. coli TP (EcTP). Compound 7 emerged as potent TP inhibitor with an IC50 value of 3.50 ± 0.01 μM. Docking studies were carried out using GOLD software on thymidine phosphorylase from human (hTP) and E. coli (EcTP). Various hydrogen bonding, hydrophobic interactions, and π-π stacking were observed between designed molecules and the active site amino acid residues of the studied enzymes.
Due to the interestingly tolerated physicochemical properties of deep eutectic solvents (DESs), they are currently in the process of becoming widely used in many fields of science. Herein, we present a novel Hg(2+) adsorbent that is based on carbon nanotubes (CNTs) functionalized by DESs. A DES formed from tetra-n-butyl ammonium bromide (TBAB) and glycerol (Gly) was used as a functionalization agent for CNTs. This novel adsorbent was characterized using Raman spectroscopy, Fourier transform infrared (FTIR) spectroscopy, XRD, FESEM, EDX, BET surface area, and Zeta potential. Later, Hg(2+) adsorption conditions were optimized using response surface methodology (RSM). A pseudo-second order model accurately described the adsorption of Hg(2+). The Langmuir and Freundlich isotherm models described the absorption of Hg(2+) on the novel adsorbent with acceptable accuracy. The maximum adsorption capacity was found to be 177.76mg/g.
The title phenyl-hydrazine derivative, C16H16N2O4, has a crystallographically imposed centre of symmetry. Except for the methyl group, all non-H atoms are almost coplanar (r.m.s. deviation = 0.0095 Å). Intra-molecular O-H⋯N hydrogen bonds are observed, generating S(6) graph-set ring motifs.
The title compound, C(15)H(14)N(2)O(5)·CH(3)OH, displays an E conformation about the azomethine double bond [C=N = 1.277 (2) Å] and the benzene rings are inclined to one another by 18.28 (9)°. An intra-molecular O-H⋯O hydrogen bond occurs between the para-OH group and one of the meta-O atoms of the 3,4,5-trihy-droxy-benzyl-idene group. In the crystal, the components are linked into a three dimensional network by O-H⋯O, O-H⋯N and C-H⋯O hydrogen bonds.
Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. Beside these α-glucosidase inhibitors has been also used as anti-obesity and anti-viral drugs. Keeping in view the greater importance of α-glucosidase inhibitors here in this study we are presenting oxindole based oxadiazoles hybrid analogs (1-20) synthesis, characterized by different spectroscopic techniques including 1H NMR and EI-MS and their α-glucosidase inhibitory activity. All compounds were found potent inhibitors for the enzyme with IC50 values ranging between 1.25 ± 0.05 and 268.36 ± 4.22 µM when compared with the standard drug acarbose having IC50 value 895.09 ± 2.04 µM. Our study identifies novel series of potent α-glucosidase inhibitors and further investigation on this may led to the lead compounds. A structure activity relationship has been established for all compounds. The interactions of the active compounds and enzyme active site were established with the help of molecular docking studies.
Due to the great biological importance of β-glucuronidase inhibitors, here in this study, we have synthesized a library of novel benzothiazole derivatives (1-30), characterized by different spectroscopic methods and evaluated for β-glucuronidase inhibitory potential. Among the series sixteen compounds i.e.1-6, 8, 9, 11, 14, 15, 20-23 and 26 showed outstanding inhibitory potential with IC50 value ranging in between 16.50 ± 0.26 and 59.45 ± 1.12 when compared with standard d-Saccharic acid 1,4-lactone (48.4 ± 1.25 µM). Except compound 8 and 23 all active analogs showed better potential than the standard. Structure activity relationship has been established.
The ability of human serum albumin (HSA) to bind medium-sized hydrophobic molecules is important for the distribution, metabolism, and efficacy of many drugs. Herein, the interaction between pyrene, a hydrophobic fluorescent probe, and HSA was thoroughly investigated using steady-state and time-resolved fluorescence techniques, ligand docking, and molecular dynamics (MD) simulations. A slight quenching of the fluorescence signal from Trp214 (the sole tryptophan residue in the protein) in the presence of pyrene was used to determine the ligand binding site in the protein, using Förster's resonance energy transfer (FRET) theory. The estimated FRET apparent distance between pyrene and Trp214 was 27Å, which was closely reproduced by the docking analysis (29Å) and MD simulation (32Å). The highest affinity site for pyrene was found to be in subdomain IB from the docking results. The calculated equilibrium structure of the complex using MD simulation shows that the ligand is largely stabilized by hydrophobic interaction with Phe165, Phe127, and the nonpolar moieties of Tyr138 and Tyr161. The fluorescence vibronic peak ratio I1/I3 of bound pyrene inside HSA indicates the presence of polar effect in the local environment of pyrene which is less than that of free pyrene in buffer. This was clarified by the MD simulation results in which an average of 5.7 water molecules were found within 0.5nm of pyrene in the binding site. Comparing the fluorescence signals and lifetimes of pyrene inside HSA to that free in buffer, the high tendency of pyrene to form dimer was almost completely suppressed inside HSA, indicating a high selectivity of the binding pocket toward pyrene monomer. The current results emphasize the ability of HSA, as a major carrier of several drugs and ligands in blood, to bind hydrophobic molecules in cavities other than subdomain IIA which is known to bind most hydrophobic drugs. This ability stems from the nature of the amino acids forming the binding sites of the protein that can easily adapt their shape to accommodate a variety of molecular structures.
This article describes discovery of 29 novel bisindolylmethanes consisting of thiourea moiety, which had been synthesized through three steps. These novel bisindolylmethane derivatives evaluated for their potential inhibitory activity against carbonic anhydrase (CA) II. The results for in vitro assay of carbonic anhydrase II inhibition activity showed that some of the compounds are capable of suppressing the activity of carbonic anhydrase II. Bisindoles having halogen at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. Derivatives showing inhibition activity docked to further, understand the binding behavior of these compounds with carbonic anhydrase II. Docking studies for the active compound 3j showed that nitro substituent at para position fits into the core of the active site. The nitro substituent of compound 3j is capable of interacting with Zn ion. This interaction believed to be the main factor causing inhibition activity to take place.
Oxadiazole derivatives (6-28) having hydrazone linkage, were synthesized through condensation reaction between benzohydrazide 5 with various benzaldehydes. The oxadiazoles derivatives (6-28) were evaluated for their α-glucosidase inhibitory activity. The IC50 values for inhibition activity vary in the range between 2.64 ± 0.05 and 460.14 ± 3.25 μM. The IC50 values were being compared to the standard acarbose (IC50=856.45 ± 5.60 μM) and it was found that compounds 6-9, 12, 13, 16, 18, 20, 22-28 were found to be more active than acarbose, while other compounds showed no activity. Structure-activity relationship (SAR) studies suggest that oxadiazole benzohydrazones (6-28) inhibitory potential is dependent on substitution of the N-benzylidene part. Compound 18 (IC50=2.64 ± 0.05 μM), which has trihydroxy substitution at C-2', C-4', and C-5' on N-benzylidene moiety, recorded the highest inhibition activity that is three-hundred times more active than the standard drug, acarbose (IC50=856.45 ± 5.60 μM). Compound 23 (IC50=34.64 ± 0.35 μM) was found to be the most active among compounds having single hydroxyl substitution. Shifting hydroxyl from C-2' to C-4' (6) and C-3' (7) reduces inhibitory activity significantly. Compounds with chlorine substituent (compounds 16, 28, and 27) showed potent activities but lower as compared to hydroxyl analogs. Substituent like nitro or methyl groups at any position suppresses enzyme inhibition activity. This reveals the important presence of hydroxyl and halo groups to have enzyme inhibitory potential.
Twenty derivatives of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles (1-20) were synthesized and evaluated for their α-glucosidase inhibitory activities. Compounds containing hydroxyl and halogens (1-6, and 8-18) were found to be five to seventy folds more active with IC50 values in the range of 12.75±0.10-162.05±1.65μM, in comparison with the standard drug, acarbose (IC50=856.45±5.60μM). Current study explores the α-glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction.
Nigella sativa is also known for its properties as a traditional herbal healing for many ailments. In this study, the anticancer properties of thyomquinone (TQ), the active ingredient of N. sativa, were studied using ovarian cancer cell line (Caov-3 cells). The anti-proliferative activity of TQ was determined using MTT and the apoptosis was investigated using Flowcytometry and Annexin-V Assays. Multiparameteric cytotoxicity bioassays were used to quantify the changes in cell permeability and mitochondrial membrane potential. Reactive oxygen species (ROS) and apoptosis-involved cell markers were examined to verify cell death mechanism. The MTT-assay showed that TQ induces anti-proliferative activity on Caov-3 with an IC50 of 6.0±0.03 μg/mL, without any cytotoxic activity towards WRL-68 normal hepatocytes. A significant induction of early phase of apoptosis was shown by annexin-V analysis. Treatment of Caov-3 cells with TQ induces decreases in plasma membrane permeability and mitochondrial membrane potential. Visible decrease in the nuclear area was also observed. A significant decrease is observed in Bcl-2 while Bax is down-regulated. TQ-triggered ROS-mediated has found to be associated with Hsp70 dysregulation, an indicator of oxidative injury. We found that TQ induced anti-cancer effect involves intrinsic pathway of apoptosis and cellular oxidative stress. Our results considered collectively indicated that thyomquinone may be a potential agent for ovarian cancer drug development.
Thirty N-arylidenequinoline-3-carbohydrazides (1-30) have been synthesized and evaluated against β-glucuronidase inhibitory potential. Twenty four analogs showed outstanding β-glucuronidase activity having IC50 values ranging between 2.11±0.05 and 46.14±0.95 than standard d-saccharic acid 1,4 lactone (IC50=48.4±1.25μM). Six analogs showed good β-glucuronidase activity having IC50 values ranging between 49.38±0.90 and 80.10±1.80. Structure activity relationship and the interaction of the active compounds and enzyme active site with the help of docking studies were established. Our study identifies novel series of potent β-glucuronidase inhibitors for further investigation.
Sixteen 4-hydroxycoumarin derivatives were synthesized, characterized through EI-MS and (1)H NMR and screened for urease inhibitory potential. Three compounds exhibited better urease inhibition than the standard inhibitor thiourea (IC50=21±0.11μM) while other four compounds exhibited good to moderate inhibition with IC50 values between 29.45±1.1μM and 69.53±0.9μM. Structure activity relationship was established on the basis of molecular docking studies, which helped to predict the binding interactions of the most active compounds.
Benzothiazole analogs (1-20) have been synthesized, characterized by EI-MS and (1)H NMR, and evaluated for urease inhibition activity. All compounds showed excellent urease inhibitory potential varying from 1.4±0.10 to 34.43±2.10μM when compared with standard thiourea (IC50 19.46±1.20μM). Among the series seventeen (17) analogs 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, and 18 showed outstanding urease inhibitory potential. Analogs 15 and 19 also showed good urease inhibition activity. When we compare the activity of N-phenylthiourea 20 with all substituted phenyl derivatives (1-18) we found that compound 15 showed less activity than compound 20 having 3-methoxy substituent. The binding interactions of these active analogs were confirmed through molecular docking.
Thiadiazole derivatives 1-24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC50=2.16±0.01-58.06±1.60μM as compare to standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Molecular docking study was conducted in order to establish the structure-activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques (1)H, (13)C NMR, and EIMS.
A series of compounds consisting of 25 novel oxadiazole-benzohydrazone hybrids (6-30) were synthesized through a five-step reaction sequence and evaluated for their β-glucuronidase inhibitory potential. The IC50 values of compounds 6-30 were found to be in the range of 7.14-44.16μM. Compounds 6, 7, 8, 9, 11, 13, 18, and 25 were found to be more potent than d-saccharic acid 1,4-lactone (48.4±1.25μM). These compounds were further subjected for molecular docking studies to confirm the binding mode towards human β-d-glucuronidase active site. Docking study for compound 13 (IC50=7.14±0.30μM) revealed that it adopts a binding mode that fits within the entire pocket of the binding site of β-d-glucuronidase. Compound 13 has the maximum number of hydrogens bonded to the residues of the active site as compared to the other compounds, that is, the ortho-hydroxyl group forms hydrogen bond with carboxyl side chain of Asp207 (2.1Å) and with hydroxyl group of Tyr508 (2.6Å). The other hydroxyl group forms hydrogen bond with His385 side chain (2.8Å), side chain carboxyl oxygen of Glu540 (2.2Å) and Asn450 side-chain's carboxamide NH (2.1Å).