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Decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1) inhibitors are an innovative and futuristic orally active group of antituberculosis agents. A few DprE1 inhibitors are in the clinical trial for tuberculosis (TB), including macozinone. This review highlights the discovery, developmental status, clinical studies, patents, and prospects of macozinone (MCZ). The patent and non-patent literature search was done by entering keywords such as macozinone; MCZ; PBTZ169; PBTZ-169 in Pubmed, Espacenet, Patentscope, and the USPTO databases. However, data on Sci-Finder was searched using CAS registry number: 1377239–83–2. MCZ clinical trial studies were retrieved from the clinicaltrials.gov database using the exact keywords. The chemical structure of MCZ was disclosed in 2009. Accordingly, patents/patent applications published from 2009 to June 12, 2022, have been discussed herein. MCZ and MCZ hydrochloride salt patents were granted in 2014 and 2019, respectively, in the USA. The patent literature and the clinical trial studies suggest capsule, tablet, and suspension formulations of crystalline MCZ and its hydrochloride salt as the possible and prospective dosage forms to treat TB. Some combinations of MCZ with other drugs (chloroquine, telacebec, tafenoquine, TBI-166, and sanfetrinem) with improved anti-TB efficacy have been documented. Based on the literature covered in this review article on the clinical studies and patents applied/granted to MCZ, it can be inferred that MCZ seems to be a promising DprE1 inhibitor and could help to tackle the emerging dilemma of drug-resistant either as a monotherapy or in combination with additional anti-TB agents. Furthermore, the authors anticipate the development of new combinations, salts, and polymorphs of MCZ as anti-TB agents shortly. This review article might prove beneficial to the scientific community as it summarizes chemistry, pharmacology and provides an update on the clinical studies and patents/patent applications of one of the emerging anti-TB drugs in one place. [ABSTRACT FROM AUTHOR]

Adequate reconstruction of the soft tissue defect following resection of bone tumors is challenging. Prolene mesh, despite being a useful tool, is not widely used due to the fear of deep infection. The aim of this study was to evaluate the functional outcome and complications of using a Prolene mesh in oncological reconstructions. A retrospective study was conducted in bone tumor patients with soft tissue reconstruction using Prolene mesh between January 2017 and June 2019. Functional evaluation was done using MSTS 93 score. Complications were recorded and were classified as mechanical (dislocation and extension lag) or biological failure (wound problems and deep infection). Comparison was performed between groups with and without biological failure to identify predictive variables. Of 116 patients, 68 were males and 48 were females, with median age of 22.5 years. Thirty nine patients had tumors of proximal tibia, 23 of proximal femur, 25 of proximal humerus, 24 of pelvis, and five tumors at other sites. Approximately two-thirds (62.9%) of our patients underwent endoprosthetic reconstruction while the rest underwent either biological or cement spacer reconstructions. Excellent or good functional outcomes were reported in 98.3% patients as per MSTS 93 scoring. Complications were noted in 22 patients (18.9%), of which 16 had biological failure, with four patients requiring debridement and mesh removal. Dislocation of prosthesis occurred in 2 patients of proximal femur replacement. Overall re-surgery rate was 5.1% (6 patients). There was no statistically significant difference between the groups with or without biological failure with respect to demographics, site of tumor, type of procedure, blood loss, duration of surgery and history of chemotherapy. Prolene mesh is a useful tool to reconstruct the soft tissue defects following bone tumor resections. It is readily available, reliable and provides reproducible results, with no added risk of wound complications. [ABSTRACT FROM AUTHOR]

It has been indicated in several instances that tall stature is also an important risk factor in the development of osteosarcoma. This relationship between height and osteosarcoma is substantiated even more by the increasing evidences being put forth in the recent literature on dependence of certain tumors on the growth factors and their receptors, acting through autocrine or paracrine mechanisms. There has been no study on the Indian population that attempts to define such a relationship. The primary objective of this study was to define relationship between height of patients and osteosarcoma at the time of diagnosis in the Indian population. Retrospective data was collected from the old hospital records. Height of patients at the time of diagnosis was compared with expected height of patients of the same age with reference to the standardized growth charts provided by the Indian Academy of Paediatrics. Out of 98 patients, there were 65 male and 33 female patients with M: F ratio being 1.97:1. The mean age at diagnosis was 17 (SD = 8) years with range of 5–55 years (median = 17 years). Height of the patients at the time of diagnosis was 155.18 (SD = 15.47) cm with range of 115 cm–184 cm (median = 159 cm). Overall, patients with Osteosarcoma were found to be shorter than the expected height deduced from the national growth charts. When patients were divided into two groups of those who were of growing age and those who had completed growth, results were similar. The observation that majority of patients with osteosarcoma in our study were stunted, is an important finding. It could be deduced from this observation that these patients are unable to mount the usual biological response to the overstimulated growth as part of tumorigenesis in osteosarcoma. This could point to a different scenario in the Indian population and more studies need to be carried out with larger number of patients to further elaborate on this observation. [ABSTRACT FROM AUTHOR]

Primary giant cell tumor (GCT) arising from bones of hand are rare to occur. Metacarpals are often the most common site of involvement among hand bones. There are no uniform guidelines for treatment of GCT involving metacarpals due to lack of relevant literature. To suggest a management strategy for GCT involving metacarpals. Retrospective review of cases of GCT involving metacarpals over a period of 15 years from 2005 to 2019 managed at department of Orthopaedics, All India Institute of Medical Sciences, New Delhi. A total of 12 cases of GCT involving metacarpal were included, out of which one was lost to follow-up. Four cases were recurrent, and seven were primary at the time of surgery. All the patients were operated with wide excision of the tumor. In seven patients reconstruction of the metacarpal and MCPJ was done using fibular strut graft and silastic artificial joint, while in two patients, MCPJ arthrodesis was performed using fibula and/or iliac crest bone graft. In another two patients, the MCPJ was reconstructed using reversed vascularised toe transfer. Mean follow up of the patients was 3.22 ± 2.07 years. Mean Quick DASH score at latest follow-up of patients operated with silastic joint reconstruction, reversed vascularised toe transfer and arthrodesis of MCP joints were 30.5 ± 9.5, 25 ± 2.3 and 39.8 ± 3.4 respectively. Local recurrence occurred only in one patient at one year after surgery. All the patients were pain free at latest follow-up with quite functional and cosmetically acceptable hand. Reversed vascularised metatarsal transfer has obtained better functional results compared to reconstruction with fibular grafting and silicone joint replacement but due to technical difficulties, vascularised joint transfer may not be performed in every setting and there is risk of donor site morbidities with this technique. Our strategy for the treatment of GCT involving metacarpal was to do vascularised joint transfer or arthrodesis for border digits and reconstruction with silicone joint for central digits. [ABSTRACT FROM AUTHOR]

• Chemical profiling of Omani Thymus vulgaris species was done by GC-MS analysis. • The GC-MS analysis of thyme essential oil established it to be a carvacrol chemotype. • Thyme essential oil exhibited better antimicrobial spectrum than ampicillin. • Thyme essential oil showed significant in vitro free radical scavenging activity in DPPH assay method. • In silico PASS prediction studies revealed carvacrol to possess useful bioactivities including cytotoxicity. Thyme is an evergreen shrub that has been utilized in traditional medicine and culinary packages for centuries because of its aroma and medicinal properties. The medicinal properties of thyme leaves are attributed to its volatile constituents. The study aimed to identify the volatile constituents in the oil extracted from the Thyme sp grown in Oman and to evaluate its in vitro antibacterial and antioxidant activity. Fresh Thyme leaves were collected from Muscat, Sultanate of Oman in the month of September 2018. Thyme oil was isolated from leaves by hydro-distillation. The volatile chemical constituents present in the thyme oil were analyzed by Gas Chromatograph coupled with Mass Spectrometer. The ability of isolated oil to scavenge free radicals was evaluated by an in vitro DPPH assay method while antimicrobial activity was tested against S. aureus and E. coli bacterial strains by disc diffusion method. The bioactivity of the major constituent of the oil was predicted with the help of PASS and CLC-pred software. Molecular docking studies were performed by docking server. GC–MS analysis of thyme oil revealed the presence of 11 components. Carvacrol and γ-terpinene were identified as the major volatile constituents in thyme oil. Thyme oil inhibited 71.57% of DPPH radicals at 40 µg/mL concentration. Thyme oil displayed the better antimicrobial activity than the standard drug ampicillin against both the bacteria. Antiseptic, antiinfective, reductant and antimutagenic bioactivities of carvacrol as predicted by PASS support the in vitro experimental results. CLC-pred showed carvacrol to be active against Metastatic melanoma, Oligodendroglioma and Non small cell lung cancer cell lines. The antioxidant and antimicrobial activity of Omani thyme oil could be due to its high content of carvacrol. Omani thyme oil seems to be a viable alternative source of natural antimicrobial agent(s) and warrants further studies to ascertain its therapeutic spectrum of biological studies. [ABSTRACT FROM AUTHOR]

New benzimidazole derivatives clubbed with biologically active heterocyclic moieties (4a–g, 5a–f, 8a–b & 9a–b) were designed and synthesized under microwave irradiation. Initial screening of compounds showed good to remarkable anticancer activity by NCI panel. Compound 4f exhibited significant growth inhibition and was further referred for five dose level study. The present study may result in the development of new anticancer agents in the near future. Based on the heterocyclic core of bendamustine, four series (4a–g , 5a–f , 8a–b and 9a–b) of benzimidazole derivatives were designed and synthesized starting from 4-(1 H -benzo[ d ]imidazol-2-yl)-4-oxobutanehydrazide. In the rational design of target molecules, the benzimidazole ring of bendamustine was retained and the bis-(chloroethyl) amine group (mechlorethamine) was substituted with several biologically active scaffolds such as oxadiazole, thiadiazole, and triazolo-thiadiazines, in the hope of obtaining novel cytotoxic agents with improved efficacy and safety. Cytotoxic activities of the designed analogues were carried out at the National Cancer Institute (NCI), USA, against full NCI 60 human cell lines. Among all the tested compounds, 4f (761982/1) exhibited significant antiproliferative activity and was further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM) with GI 50 values ranging from 0.09 to 16.2 μM and found superior for CNS cancer cell line SNB-75 (GI 50 0.09, TGI 1.39, LC 50 >100 and log 10 GI 50 −7.0, log 10 TGI-5.86, log 10 LC 50 >−4.00). Docking study was also performed to provide an insight about the binding mode into binding sites of topoisomerase enzyme. Hopefully in future, compound 4f could be used as a lead compound for developing new anticancer agents. [ABSTRACT FROM AUTHOR]

The primary treatment of Giant cell tumor of bone is surgical management. Bisphosphonates are antiresorptive drugs which inhibit osteoclast mediated bone resorption and shown to have inhibitory effect on various tumors. The present study aims to establish clinical, ultrastructural and radiological response of intravenous zoledronic acid on giant cell tumor of bone. Design - Prospective randomized controlled study. A group of 30 patients of GCT bone were randomized into two equal groups. Patients in control group did not receive any adjuvant therapy before surgery. Patients in bisphosphonate group received three doses of intravenous zoledronic acid at four weeks interval prior to definitive surgery. The evaluation was done based on size of swelling, VAS score, plain radiograph, MRI and histopathological and Transmission electron microscopic examination findings. Significant reduction in VAS score (from mean 5.33 to 1.8), increased mineralization particularly at periphery of lesion in plain radiograph, statistically significant increase in mean apoptotic index, P value < 0.0001 (mean 41.46 in bisphosphonate group and 6.06 in control group) was noted in bisphosphonate group. No significant change in tumor volume is noted in MRI. No significant side effects were noted. One distinctive feature of pathogenesis of GCT bone is osteoclastogenesis which causes extensive bone destruction. Use of intravenous Zoledronic acid counteracts this bone destruction. Further, possible antiangiogenic effect of intravenous bisphosphonates inhibits tumor growth and provides symptomatic improvement. IV Zoledronic acid alleviates pain, produce sclerosis and induce apoptosis hence decrease the rate of tumor progression and decrease the rate of local bone destruction, hence they are useful adjuvant to surgery in GCT. [ABSTRACT FROM AUTHOR]

Wrist reconstruction after distal radial tumor resection poses a challenge to the orthopedic oncologist. We evaluated the functional outcomes of centralization of the ulna with ulnocarpal arthrodesis as a method of reconstruction following resection of distal radius tumors, using impairment measures and patient-reported outcomes. Evaluation of functional outcome was performed using the Musculoskeletal Tumor Society 93 scoring system and Disabilities of the Arm, Shoulder, and Hand questionnaire. We also determined hand grip strength on the affected side, time to radiologic union at the ulnocarpal junction and reduction in wrist circumference. Local complications and oncologic outcomes were recorded. The study included 26 patients with Campanacci grade 3 giant cell tumor of the distal radius. Mean follow-up period in the study was 32.8 ± 12 months. Mean resection length was 10.3 ± 2.5 cm. Radiologic union at the ulnocarpal junction was achieved in 38.5%, 77% and 96% of the patients by 4, 5, and 6 months respectively. Mean hand grip strength was 74 ± 3.9% of the contralateral side whereas mean reduction in wrist circumference was 16.9 ± 6.4%. A good functional outcome with a mean the Musculoskeletal Tumor Society 93 score of 26 ± 1.4 and mean Disabilities of the Arm, Shoulder, and Hand score of 10.5 ± 6.3 was observed. Fracture of the ulna, hardware loosening, and reflex sympathetic dystrophy were each noted in 1 patient, with an overall complication rate of 10.7% (3/28). No patient had nonunion, infection, or local recurrence. This is a simple and effective modality of reconstruction after resection of distal radial tumors. It provides good functional outcome and preservation of good hand grip strength, with low complication rates. Therapeutic IV. [ABSTRACT FROM AUTHOR]

Based on the core structure of Felbinac drug, three series ( 4a – d, 5a – d and 6a – n ) of five membered heterocyclic derivatives containing three heteroatoms were designed and synthesized starting from Felbinac. In the rational design of the target molecules, the biphenyl ring along with the methylene bridge of felbinac was retained while the carboxyl group was substituted with biologically active substituents like 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole, with an intent to obtain novel, better and safer anti-inflammatory agents with improved efficacy. The prepared molecules were then investigated for their anti-inflammatory, ulcerogenicity and analgesic activity in experimental animals. The tested compounds exhibited varying degrees of inflammatory activity (25.21–72.87%), analgesic activity (27.50–65.24%) and severity index on gastric mucosa in the range of 0.20–0.80 in comparison to positive control felbinac (62.44%, 68.70% and 1.5, respectively). Among all the prepared compounds, 2-(biphenyl-4-ylmethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole ( 6c ) emerged as the most potent NSAID compound exhibiting the highest anti-inflammatory activity (72.87% inhibition) and analgesic activity (65.24%) along with the least severity index on gastric mucosa (0.20). Further, molecular docking on cyclooxygenase and in silico ADME-Toxicity prediction studies also supported the experimental biological results and indicated that 6c has a potential to serve as a drug candidate or lead compound for developing novel anti-inflammatory and analgesic therapeutic agent(s) with minimum toxicity on gastric mucosa. [ABSTRACT FROM AUTHOR]

Eslicarbazepine acetate (ESL) is a new, once daily, orally administered, third generation antiepileptic drug which is indicated in the treatment of partial-onset seizures. ESL is known to exert it's anticonvulsant effect by blocking the voltage-gated sodium channels. Several clinical trials and pharmacological studies have revealed that seizure control was better with ESL monotherapy (1 200 or 1 600 mg once daily) following a switch from other antiepileptic drugs in comparison with pseudo-placebo patients. The studies have indicated the ESL to be well tolerated and produced only mild to moderate emergent adverse events with the therapy. Being a dibenzazepine family member, structure and chemistry of ESL resembles more or less to carbamazepine and oxcarbazepine. ESL differs structurally from carbamazepine and oxcarbazepine at the 10, 11 position of dibenazepine nucleus. This molecular variation results in differences in metabolism and thus helps to prevent the formation of toxic epoxide metabolites. ESL following oral administration is rapidly metabolised to active metabolite namely S-licarbazepine which is responsible for its pharmacological activity. ESL exhibits acceptable pharmacokinetic profile and shows insignificant drug-drug interactions. In phase III clinical program, ESL was found to be efficacious and well tolerated in adult patients with partial onset seizures previously not controlled with treatment with one or two other antiepileptic drugs. [ABSTRACT FROM AUTHOR]

The pentacyclic triterpenic acids isolated from the oleo gum resin of various Boswellia species are collectively called as Boswellic acids (BA). The oleo gum resin obtained from Indian variety i.e. Boswellia serrata (Family – Burseraceae) is commonly known as Salai guggal. The resin fraction of Salai guggal is rich in Boswellic acids and its essential oil is composed of a mixture of mono, di and sesquiterpenes while gum fraction chiefly contains pentose and hexose sugars. This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine owing to their wide range of useful biological properties such as anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial anti-fungal, anti-complementary and analgesic activity, etc. It has been used as a herbal medicine since the prehistoric time to cure acute and chronic ailments including inflammatory diseases. Phytochemical investigation of this herbal medicine lead to identification of Boswellic acids which are found to be novel, potent, specific anti-inflammatory agents due to non-redox inhibition of 5-lipoxygenase (5-LO) enzyme. However, the other important targets of Boswellic acids also include topoisomerases, angiogenesis, and cytochrome p450 enzymes. This review is a sincere attempt to discuss and present the current status of therapeutic potential, phytochemical as well as pharmacological profile of Boswellic acids primarily obtained from B. serrata . [ABSTRACT FROM AUTHOR]

A small library of twenty-four quinoline based butenolides also known as furanones and their nitrogen analogues was prepared by using two different aroylpropionic acids, viz. 3-(2-naphthoyl)propionic acid ( 3 ) and 3-(biphenyl-4-yl)propionic acid ( 4 ), as starting materials. The 3-aroylpropionic acids were reacted with different 6-substituted-2-chloroquinolin-3-carbaldehydes ( 2a–d ) to obtain the corresponding furan-2(3 H )-ones ( 5a–h ). The purified and characterized furanones were then converted into their corresponding 2(3 H )-pyrrolones ( 6a–h ) and N -benzyl-pyrrol-2(3 H )-ones ( 7a–h ). The antimicrobial activities of the title compounds were evaluated against two strains of each Gram +ve ( Staphylococcus aureus and Bacillus subtilis ), Gram −ve bacteria ( Escherichia coli and Pseudomonas aeruginosa ) and against fungal strains of Aspergillus niger and Aspergillus flavus . In vivo anti-inflammatory potential of the title compounds was investigated by standard method. Majority of the compounds showed significant antibacterial activity against both the Gram +ve strains. Eight most potent anti-inflammatory compounds ( 5b, 5d, 5h, 6b, 7b, 7d, 7f, 7h) which exhibited >53% inhibition in edema, were also screened for their in vivo analgesic activity. All the tested compounds were found to have significant reduction in ulcerogenic action but only three compounds ( 5d, 5h and 7h ) showed comparable analgesic activity to standard drug, diclofenac. The results were also validated using in silico approach and maximum mol doc score was obtained for compounds 7a–h . On comparing the in vivo and in silico anti-inflammatory results of synthesized compounds, N -benzyl pyrrolones ( 7a–h ) emerged as the potent anti-inflammatory agents. It was also observed that compounds that possess electron withdrawing group such as Cl or NO 2 are more biologically active. [ABSTRACT FROM AUTHOR]

In the present study, two new series of pyrazolines ( 3a – h & 4a – h ) were synthesized starting from p -acetamidophenol (paracetamol) and evaluated for their antibacterial, antifungal and antitubercular activities. Chalcones ( 2a – h ) prepared by condensing 3-acetyl-4-hydroxyphenyl acetamide ( 1 ) with different aromatic aldehydes were reacted with phenyl hydrazine and isonicotinic acid hydrazide to obtain phenyl-pyrazolines ( 3a – h ) and isoniazid-pyrazolines ( 4a – h ), respectively. The structures of the synthesized compounds were confirmed by spectral and microanalysis studies. Newly prepared pyrazoline compounds exhibited significant antibacterial activity against the organisms Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa when compared with the standard antibiotic Ciprofloxacin. Compound 4g showed potent antibacterial activity against P. aeruginosa and S. aureus (MIC-3.12 μg/mL), however, against E. coli compound 3d , 4c , 4d , 4f & 4g were found to have an MIC of 6.25 μg/mL. Antifungal activity of compound 4d against Candida albicans and Aspergillus niger (MIC-3.12 μg/mL) was found to be better than the standard drug Ketoconazole. The results of antitubercular activity of the synthesized compounds against Mycobacterium tuberculosis H 37 Rv by the agar microdilution method are quite promising. The antitubercular activity of compounds 4c , 4d & 4g (MIC-3.12 μg/mL) was found to be superior than that of the reference drug Streptomycin which showed MIC equal to 6.25 μg/mL. It was observed that pyrazolines with chloro, nitro or methoxy substituent showed better activity. Also, the pyrazolines derived from isoniazid ( 4a – h ) were found to be better in their antibacterial, antifungal and antitubercular action than those derived from phenyl-hydrazine ( 3a – h ). [ABSTRACT FROM AUTHOR]

Giant cell tumor (GCT) of bone is a benign locally aggressive tumor whose biological behavior is unpredictable. Currently, there are no definitive clinical, histological, biochemical, or immunological parameters that can predict its behavior. This study was undertaken to examine whether delineation of reactive and neoplastic stromal component of GCT can help in this regard. 55 cases of GCT (30 primary, 25 recurrent) were subjected to histopathological grading, immunohistochemistry, and image analysis. Spindling of stroma was more frequent in recurrent GCT with 64% cases having more than 50% spindled stroma ( p < 0.001). Number of mitosis/10 HPF and higher grade were more in recurrent GCT. Mean percentage positivity for CD68 (38.36%) and α1-ACT (70.86%) was higher in primary than recurrent GCT. PCNA and MiB-1 labeling indices were higher in recurrent (42.62% and 9.18%, respectively) than in primary group (24.75% and 7.7%, respectively). A single numerical parameter encompassing stromal cell population and its proliferation was derived as ratio of PCNA/CD68 and PCNA/α1-ACT. Both ratios were higher in recurrent (0.81 ± 0.38; 1.58 ± 1.50) than in primary GCT (0.58 ± 0.62; 0.34 ± 0.29) ( p = 0.002; 0.01). On image analysis, parameters significantly different between the two groups were nuclear area and nuclear integrated optical density. It was thus concluded that recurrent GCT shows higher grade, increased mitosis, more spindling, fewer reactive components, and higher proliferation than primary GCT. Delineation of reactive component (α1-ACT positive) and proliferating component (PCNA positive cells) using immunohistochemistry with calculation of the PCNA/ACT ratio delivers more information than image analysis. [ABSTRACT FROM AUTHOR]

Objective To evaluate and compare the antioxidant activity, total phenolic contents (TPCs) and in vitro antidiabetic activity of various pits extracts obtained from five Omani date cultivars. Methods Sun-dried mature fruits of five Omani date varieties, namely, Fardh, Naghal, Khalas, Khinazi and Khasab were purchased from the local market in Muscat, Oman in the month of September 2014. Four seed extracts viz. water, ethanol, methanol and acetone were prepared for each date variety and their antioxidant activities were investigated by 1,1-diphenyl-2-picrylhydrazyl, hydrogen peroxide scavenging method and reducing power assay method, respectively. In vitro antidiabetic activity of the date pit extracts was evaluated by measuring their inhibitory effect on α-glucosidase and α-amylase level. TPCs were also quantified colorimetrically. Results The results indicated that TPC of date seeds was solvent dependent. Acetone, ethanol and methanol were found to be significantly better solvents than water in extracting phenolic compounds from the date seeds. Pit extracts exhibited moderate to good in vitro antioxidant activity and increased reducing power. Among all date pit extracts, water extract exhibited significant in vitro antidiabetic activity in comparison to standard drug, acarbose. Conclusions The present study confirms that disposed waste of Omani dates is a rich source of dietary antioxidant because of its high TPC. The pits due to their inhibitory effects on α-glucosidase and α-amylase level could be used as a monotherapy along with an appropriate diabetic diet and exercise or might be in conjunction with antidiabetic therapy to manage and prevent progression of diabetes. [ABSTRACT FROM AUTHOR]

Dronedarone, a benzofuran containing chemical compound, is a derivative of amiodarone which is classified as a Class III antiarrhythmic agent. It is prescribed to the cardiovascular patients who have paroxysmal or persistent atrial fibrillation to lower the chances of hospitalization. Amiodarone, sotalol, procainamide dofetilide, quinidine, ibutilide, flecainide, and propafenone are the other useful medicinal products used to treat atrial fibrillation or cardiac arrhythmia. Dronedarone was approved for clinical use in atrial fibrillation by the Food and Drug Administration in 2009. The generic name for dronedarone is Multaq (Sanofi Aventis). This article briefly highlights the important pharmacological, pharmacodynamic and pharmacokinetic properties of dronedarone. [ABSTRACT FROM AUTHOR]

The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives ( 3a–k ) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives ( 3a–k ) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine ( 3g ), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine ( 3i ) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine ( 3j ) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number ( 3i) emerged as a potential candidate for further research as it obeyed Lipinski’s rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. [ABSTRACT FROM AUTHOR]

Nowadays, use of alternative and complementary therapies with mainstream medicine has gained the momentum. Aromatherapy is one of the complementary therapies which use essential oils as the major therapeutic agents to treat several diseases. The essential or volatile oils are extracted from the flowers, barks, stem, leaves, roots, fruits and other parts of the plant by various methods. It came into existence after the scientists deciphered the antiseptic and skin permeability properties of essential oils. Inhalation, local application and baths are the major methods used in aromatherapy that utilize these oils to penetrate the human skin surface with marked aura. Once the oils are in the system, they remodulate themselves and work in a friendly manner at the site of malfunction or at the affected area. This type of therapy utilizes various permutation and combinations to get relief from numerous ailments like depression, indigestion, headache, insomnia, muscular pain, respiratory problems, skin ailments, swollen joints, urine associated complications etc. The essential oils are found to be more beneficial when other aspects of life and diet are given due consideration. This review explores the information available in the literature regarding therapeutic, medical, cosmetic, psychological, olfactory, massage aromatherapy, safety issues and different plants used in aromatherapy. All the available information was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubMed, Science Direct, Web of Science, and library search. [ABSTRACT FROM AUTHOR]

In continuation of our research on nitrogen containing heterocyclic compounds to develop potent antimicrobial and antimycobacterial agents, some novel 2( 3H ) pyrrolone derivatives were synthesized. We report here two new series of 3-Arylidene-5-(4-chloro/methyl phenyl)-2( 3H ) pyrrolones ( 14 – 19 ) and 3-Arylidene-5-(4-chloro/methyl phenyl)-1-benzyl-2( 3H ) pyrrolones ( 20 – 25 ) prepared by reacting intermediate furanone compounds ( 6 – 13 ) with ammonia gas and benzylamine respectively. The structures of the title compounds were established on the basis of IR, 1 H NMR, mass spectral data and elemental analysis results. All the synthesized pyrrolone derivatives were evaluated for their possible antibacterial, antifungal and antitubercular activities. Among all the synthesized compounds, compound 17 , 3-(4-Hydroxy-3-methoxybenzylidene)-5-(4-chlorophenyl)-2(3 H )-pyrrolone, emerged as a lead compound exhibiting the highest antibacterial, antifungal and antitubercular activity against Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa and Mycobacterium tuberculosis with 6.25 μg/mL MIC (minimum inhibitory concentration). Molecular properties of pyrrolones were also calculated by Molinspiration software for drug likeness. It was observed that all 2( 3H ) pyrrolones ( 14 – 19 ) obeyed Lippinski’s rule of five and expected to be orally active. They were also found to be more potent antimicrobial agents than 1-benzyl-2( 3H ) pyrrolones ( 20 – 25 ) and their activity was comparable with standard drugs such as Ciprofloxacin, Ketoconazole and Streptomycin. [ABSTRACT FROM AUTHOR]

Objective: To carry out the physicochemical and phytochemical standardization with high performance thin layer chromatography fingerprinting of Piper nigrum L. ( P. nigrum ) fruits in order to ascertain the standard pharmacognostical parameters of this king of spices. Methods: Many standardization parameters like extractive values, total ash value, water soluble ash value and acid insoluble ash, moisture content, loss on drying and pH values of P. nigrum L. fruits were analyzed. The method of Harborne was adopted for the preliminary phytochemicals screening. Analysis of total phenolic and flavonoid contents, pesticides residues, aflatoxin and heavy metals were also performed. CAMAG-high performance thin layer chromatography system was used for fingerprinting of methanolic extract of P. nigrum L. fruits. Results: The results of phytochemicals testing indicated the presence of carbohydrates, phenolic compounds, flavonoids, alkaloids, proteins, saponins, lipids, sterols and tannins in various solvent extracts. Total phenolic and flavonoid contents in methanolic extract were found to be 1.728 1 mg/g and 1.087 μg/g, respectively. Heavy metals concentrations were found to be within standard limits. Aflatoxins and pesticides residues were absent. Conclusions: The outcome of this study might prove beneficial in herbal industries for identification, purification and standardization of P. nigrum L. fruits. [ABSTRACT FROM AUTHOR]

Background The prevalence of diabetes mellitus (DM) has increased alarmingly mainly due to the life style changes and obesity factor. Approximately 10% of the Omani population is suffering from this chronic disease and according to World Health Organization, number of subjects living with diabetes in Oman will rise from 75,000 in 2000 to 217,000 in 2025. It has been well established that data on KP of diabetic patients reveal aspects of education that need to be reinforced and addressed in order to improve diabetes management. Objective The aim of this cross sectional study was to assess the diabetes mellitus type 2 related knowledge and practices (KP) of Omani adult patients. Materials and methods Diabetic patients were recruited using the convenient sampling method from Outpatient diabetes clinic of various primary health care centers and private hospitals in Muscat region of Sultanate of Oman. KP of patients who agreed to participate in the study were assessed by administering a self designed questionnaire containing 15 close ended or multiple choice type questions in face-to face interviews. The collected data were analyzed by SPSS software. Results and discussion 106 patients with T2DM participated in this study (42 men and 64 women). Majority of them were; married (83%), above 50 years (64.2%), on oral hypoglycemic (56.6%), having family history of diabetes (66%). The mean ± SD knowledge score of participants was found to be 4.92 ± 1.22 out of maximum possible score of 8. Conclusion Omani patients seemed aware and displayed satisfactory diabetes knowledge and good practices except adherence to regular exercise. We recommend to design and develop diabetes educational programs that could help Omani patients in diabetes management and improvement of quality of life. [ABSTRACT FROM AUTHOR]

Objective To perform phytochemical screening, estimate total phenolics, flavonoids and to evaluate antioxidant potential of Moringa peregrina ( M. peregrina ) leaves. Methods The dried powdered leaves of M. peregrina (150 g) were extracted exhaustively by Soxhlet with ethanol and then fractionated into hexane, chloroform, ethy alacetate and methanol. All the prepared extracts were also analyzed by gas chromatography-mass spectrometry to identify and characterize the chemical compounds present in the crude extracts. Folin- Ciocalteu reagent and aluminium chloride colorimetric methods were used to estimate total phenolic and flavonoid content of extracts. Hydrogen peroxide and 1,1 diphenyl -2-picrylhydrazyl were used to determine in vitro antioxidant activity. Results Phytochemical analysis of ethanol extract showed presence of major classes of phytochemicals. Gas chromatography-mass spectrometry results revealed presence of 19 phytoconstituents in hexane extract, 6 in ethyl acetate and 7 compounds in methanolic extract. Methanol extract was found to contain the highest phenolic content and flavonoids. In vitro antioxidant activities of all crude extracts were significant and comparable with the standard ascorbic acid. Conclusions Results of this study show that the leaves of M. peregrina are the rich source of phenolic compounds that can play an important role in preventing the progression of many diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] The study aimed to synthesize and evaluate the potential anti-inflammatory and analgesic activities of rationally designed hybrid molecules of imidazolone and indole nuclei linked through a methylene bridge. Indolyl-imidazolone hybrids were synthesized in three simple steps starting from 2-phenyl-1 H -indole (1). In the first step, compound 1 was converted to 2-phenyl-1 H -indole-3-carbaldehyde (2) using standard conditions of the Vilsmeier Haack reaction. Benzoyl glycine was reacted with 2 (step 2) followed by treatment with aromatic/aliphatic amines (step 3) to furnish the indolyl-imidazolone hybrids. In vivo anti-inflammatory and analgesic activity along with ulcerogenicity of the prepared hybrids were evaluated in experimental animals. Molecular properties and pharmacokinetic profile were also predicted using online computational software. Cyclooxygenase-2 (COX-2) enzyme (PDB: 3pgh) was used for molecular docking studies. Indomethacin and aspirin were used as reference compounds for the comparison purpose. The percentage inhibition in edema in rats and reduction in frequency of acetic acid induced writhes in mice indicated that two compounds namely 3-(3-Hydroxpropyl)-2-phenyl-5-[(2-phenyl-1 H -indol-3-yl)methylene]-4 H -imidazol-4-one (4g) and 3-(2,4-Dinitrophenyl)-2-phenyl-5-[(2-phenyl-1 H -indol-3-yl) methylene]- 4 H -imidazol-4-one (4b) could be useful in treating pain and inflammatory conditions. Both the hybrid molecules exhibited better biological spectrum than the standard drug indomethacin. Additionally, both the potent compounds were noted to be less ulcerogenic than indomethacin. Pharmacokinetic profile predicted using ADMETsar and SwissADME cheminformatic software indicated compound 4g to be orally bioavailable with high blood brain barrier permeability. However, molecular docking studies revealed that compound 4b binds to COX-2 enzyme more strongly than 4g as indicated by a lower binding energy and formation of hydrogen bond interactions with amino acid residues in the binding pocket. It could be concluded that hybrid compounds 4b and 4g are promising lead candidates and should be further studied to develop compounds for the treatment of inflammatory conditions. [ABSTRACT FROM AUTHOR]

[Display omitted] Alzheimer's disease (AD) is one of the most common and prevalent forms of neurodegenerative diseases. Coumarin is a versatile scaffold that exhibits a wide range of biological properties including cholinesterase inhibitory activity and therefore is an important heterocyclic moiety to develop anti-AD drugs. This study aimed to design and synthesize coumarin linked 1,3,4-oxadiazole hybrid derivatives as multi-target directed ligands (MTDLs) and to investigate their in vitro anticholinesterase, antioxidant and anti-inflammatory activities. Two series (4a-n and 7a-m) of low molecular weight ligands (27 compounds) containing coumarin linked 1,3,4-oxadiazole hybrids were synthesized and their chemical structures were characterized using analytical data. In vitro acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) inhibitory activity, antioxidant activity and cyclooxygenase (COX) inhibitory activity were investigated following standard spectrophotometric methods. Molecular docking studies to predict the binding mode with AChE and BuChE in addition to the pharmacokinetic profile of the synthesized compounds were studied with the help of online cheminformatics software. Amongst the tested compounds for anticholinesterase activity, 4e and 4g hybrid derivatives were found to be the most potent AChE inhibitors (IC 50 values = 29.56 and 28.68 μM), respectively. Compound 4m exhibited the maximum inhibitory activity against BuChE (IC 50 value = 23.97 μM). Compounds 4g and 4e also showed higher selectivity index (SI) of 1.652 and 1.552 as compared to standard galantamine (SI = 1.132). Molecular docking studies revealed that 4g and 4e, two most potent AChE inhibitors identified through in vitro assay, binds well to AChE (binding energy scores of −9.7 and −10.1 Kcal/Mol). Synthesized hybrid molecules also exhibited good to excellent in vitro antioxidant and anti-inflammatory activities. Based on the results of in vitro and in-silico studies, it could be concluded that coumarin-oxadiazole hybrids acts as MTDLs and are promising source of anti-AD drugs. Further detailed investigations and modification of these compounds can lead to the development of highly potent therapeutics for the treatment of AD. [ABSTRACT FROM AUTHOR]

Objective To evaluate the practices of university students towards self-medication to treat minor ailments in Muscat and Sohar region of Sultanate of Oman. Methods A cross sectional study was conducted in October 2013-January 2014. A total of 450 university students were randomly selected and their verbal consent was obtained. The data were collected through the self-administered, close ended, pretested questionnaire and was analyzed statistically by SPSS version 19.0. Results Overall 204 males (45.3%) and 246 females (56.7%) participated in the study. The mean age of respondents was 22.3 years. Ninety-four percent of respondents reported practicing self-medication and 165 (36.7%) participants admitted of having purchased drugs without prescription more than four times over the last six months. Headache, fever, cough and cold were the most common ailments which prompted respondents to seek self-medication. Analgesics, cough preparations and antibiotics were the most common classes of drugs used in self-medication. The majority of respondents practiced self-medication either because their illness was not serious or they had prior experience with the drug. The majority of respondents had good medication knowledge which they reported to acquire from reading drug leaflet or from pharmacists' advice. Conclusion The prevalence of self-medication among university students was very high. There is a need for intensive education and comprehensive awareness campaign to advocate for reduction in the prevalence of self-medication practices among students. [ABSTRACT FROM AUTHOR]

Abstract: Schwannomas of osseous origin are rare, and schwannomas of the short tubular bones are even rarer. These benign-looking tumors are difficult to diagnose using imaging alone. However, histopathologic evaluation of a biopsy specimen can establish the diagnosis by identifying Antoni type A and B zones. Curettage and bone grafting will probably be adequate for treatment because malignant changes are unlikely. Large lesions can require en bloc excision and reconstruction. We describe what appears to be only the second case of a schwannoma in the first metatarsal of the foot in a 48-year-old woman. The lesion was poorly contained, with obvious breaks in the cortical shell. The diagnosis was confirmed by pathologic analysis. The lesion was successfully treated with en bloc resection and reconstruction with a nonvascularized fibular graft. [Copyright &y& Elsevier]

Background: Epithelioid hemangioma (EH) is a rare benign vascular lesion of soft tissue and bone, characterized by endothelial cells with epithelioid or histiocytoid appearance. Though tubular bones, fat bones, vertebra and short bones are common sites for this lesion, the epiphyseal involvement is extremely rare. We present an unusual case of EH of the distal femur in a young boy. Case report: A 12-year-old boy who had congenital talipes equinovarus of the right foot presented with progressively increasing pain in the right lower thigh for six months. Physical examination revealed muscular atrophy of the right lower limb and a moderately tender swelling in the medial aspect of the right knee without restriction of knee movement. An X-ray revealed an osteolytic lesion, which appeared iso- and hypointense on T1W and hyperintense on T2W MRI images in the distal epiphysis and adjacent metaphysis of the right femur. A radiological diagnosis of chondroblastoma was entertained. The patient was treated with curettage and bone grafting. Histopathology showed a tumor composed of thin-walled arteriolar capillaries lined by large, polyhedral epithelioid endothelial cells with vesicular nuclei, finely distributed nuclear chromatin, and moderate amount of eosinophilic cytoplasm. The endothelial cells were strongly immunopositive for CD34. Mitotic activity was low and the Ki-67 proliferative rate was <2%. A diagnosis of EH was made. EH is a benign lesion and it should be differentiated from its histologically similar malignant counterparts such as epithelioid hemangioendothelioma and epithelioid angiosarcoma as the lesion can be successfully treated with curettage or resection. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate and compare the antioxidant potential and anti–inflammatory activity of ethanolic extract of flowers of Moringa oleifera (M. oleifera) grown in Oman. Methods: Flowers of M. oleifera were collected in the month of December 2012 and identified by a botanist. Alcoholic extract of the dry pulverized flowers of M. oleifera were obtained by cold maceration method. The ethanolic flower extract was subjected to preliminary phytochemical screening as the reported methods. Folin–Ciocalteu reagent was used to estimate total phenolic content. DPPH was used to determine in–vitro antioxidant activity and anti–inflammatory activity of flowers was investigated by protein denaturation method. Results: Phytochemical analysis of extract showed presence of major classes of phytochemicals such as tannins, alkaloids, flavonoids, cardiac glycosides etc. M. oleifera flowers were found to contain 19.31 mg/g of gallic acid equivalent of total phenolics in dry extract but exhibited moderate antioxidant activity. The anti–inflammatory activity of plant extract was significant and comparable with the standard drug diclofenac sodium. Conclusions: The results of our study suggest that flowers of M. oleifera possess potent anti–inflammatory activity and are also a good source of natural antioxidants. Further study is needed to identify the chemical compounds responsible for their anti–inflammatory activity. [Copyright &y& Elsevier]

Abstract: Nigella sativa (N. sativa) (Family Ranunculaceae) is a widely used medicinal plant throughout the world. It is very popular in various traditional systems of medicine like Unani and Tibb, Ayurveda and Siddha. Seeds and oil have a long history of folklore usage in various systems of medicines and food. The seeds of N. sativa have been widely used in the treatment of different diseases and ailments. In Islamic literature, it is considered as one of the greatest forms of healing medicine. It has been recommended for using on regular basis in Tibb-e-Nabwi (Prophetic Medicine). It has been widely used as antihypertensive, liver tonics, diuretics, digestive, anti-diarrheal, appetite stimulant, analgesics, anti-bacterial and in skin disorders. Extensive studies on N. sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, etc. Due to its miraculous power of healing, N. sativa has got the place among the top ranked evidence based herbal medicines. This is also revealed that most of the therapeutic properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil. The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics, chemical composition and pharmacological activities of the seeds of this plant. [Copyright &y& Elsevier]

Objective: To present our experience in treatment of difficult ununited long bone fractures with locking plate.Methods: Retrospective evaluation of locking plate fixation in 10 difficult nonunions of long bone fractures was done. Fixation was done with locking plate for femoral shaft fracture (3 patients), supracondylar fracture of femur (gap nonunion), fracture of clavicle, fracture of both forearm bones (radius and ulna) fracture of ulna, fracture of shaft of humerus, fracture of tibial diaphysis and supracondylar fracture of humerus (one patient each). Five fractures had more than one previous failed internal fixation. One patient had infected nonunion which was managed by debridement with cast immobilization followed by fixation with locking plate at six weeks. Seven fractures were atrophic, two were oligotrophic, and one was hypertrophic. Fibular autograft was used in 2 cases and iliac crest cancellous bone graft used in all the patients.Results: Minimum follow-up was 6 months (range, 6 months to 2.5 years). Average time for union was 3.4 months (range 2.5 to 6 months). None of the patients had plate-related complications or postoperative wound infections.Conclusion: Along with achieving stability with locking compression plate, meticulous soft tissue dissection, acceptable reduction, good fixation technique and bone grafting can help achieve union in difficult nonunion cases. Though locking plate does not by itself ensure bony union, we have found it to be another useful addition to our armamentarium for treating difficult fracture nonunions. [ABSTRACT FROM AUTHOR]

Pigmented villo-nodular synovitis (PVNS) is a common disease entity particularly in the knee joint but its incidence in the foot is quite rare. A case of PVNS of the second toe that presented at the outpatient department with an insidious onset and slowly progressive painful swelling of the toe associated with stiffness is presented. The mass was subsequently excised and the diagnosis confirmed by histo-pathology samples. The patient’s symptoms improved significantly after the operation. This case is one of the very few reported cases of PVNS involvement of flexor tendon sheath of the foot. It also signifies the importance of clinical suspicions based on the symptoms and examination in reaching to the presumptive diagnosis of the foot pathology and its confirmation by histo-pathological evaluation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disease. Punica granatum L., (P. granatum) is one of the most important commercial crops of Oman with traditional medicinal claims. The study aimed to quantify the phenolic content of the Omani pomegranate peel extracts and to investigate their antioxidant, anti-cholinesterase activities along with computational studies for the development of AD therapy. The dried peels of P. granatum fruits were exhaustively extracted with chloroform, ethyl acetate and butanol. Peel extracts were subjected to the preliminary phytochemical screening. Colorimetric methods were used to quantify total phenolic and flavonoids contents. The neuroprotective potential of the peel extracts was evaluated by assessing the in-vitro antioxidant activity and their ability to inhibit acetylcholinesterase (AChE) enzyme activity. In-silico analysis and molecular docking of the most promising phenolic metabolite present in pomegranate peel was also carried out. The phytochemical screening showed the presence of flavonoids, tannins, alkaloids, carbohydrates and terpenoids. The total phenolic, flavonoids content & antioxidant activity was found to be higher in the butanol extract. Surprisingly, butanol extract showed slightly lower AChE inhibitory activity than chloroform extract. Catechin, a polyphenolic compound present in the peel showed lower binding energy for AChE in comparison to Beta-secretase-1 (BACE-1). It formed three and two hydrogen bonds with AChE and BACE-1, respectively. The results of the current study provided evidence that butanol extract is rich in phenolics and possesses excellent antioxidant activity. Furthermore, in silico and in-vitro studies conducted on P. granatum revealed promising anti-AD activity. Further investigations must be carried out to isolate and develop the chemical constituents of pomegranate peel as neuroprotective agent(s). [Display omitted] • Phytochemical screening and quantification of phenolic compounds in an agro-waste. • Evaluation of antioxidant and anticholinesterase activity of pomegranate peel extracts. • In silico studies and molecular docking studies on the polyphenolic compounds found in pomegranate peel. • Butanol solvent was found to be optimum for the isolation of polyphenolic compounds. • Pomegranate peel could be used as an alternative source of natural antioxidants. [ABSTRACT FROM AUTHOR]