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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]

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]

Furanone, a five-membered heteroaromatic ring containing oxygen atom, is of immense pharmaceutical importance. Presence of this nucleus in biologically active compounds of natural and synthetic origin has made it an indispensable motif for design and development of new therapeutic agents. In recent years synthesis of furanone derivatives and exploring their therapeutic actions has been the prime interest amongst researchers. Furanone containing compounds cover numerous therapeutic categories viz. Analgesic and anti-inflammatory, anticancer, anticonvulsant, antibacterial and antifungal, antioxidant, antiulcer and anti-TB, etc. There is a need to couple recent work done with previously available information on furanone, a well acknowledged scaffold, to help scientists to develop novel and new furanone based therapeutic agents at a faster pace. This updated review highlights the worth of numerous therapeutically active furanone based compounds developed by the medicinal chemists. SAR studies have also been derived which may be useful for rational designing of furanone derivatives with improved therapeutic index. Image 1 • 2(5H) furanone derivatives emerged as the most promising anti-inflammatory, anti-cancer and anti-microbial agents. • The review covers useful pharmacological activities of furanone derivatives along with SAR studies. • It provides an overview of research work carried out on furanones in past three decades. • Enlist the patents granted on furanones and drugs containing furanone nucleus. [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]

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]

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]

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]

The study aimed to characterize the volatile constituents of Mentha spicata L., grown in Oman, and to investigate in vitro cytotoxic and antioxidant activities of the volatile oil. The pale-yellow color essential oil (% yield 0.55% v/w) showed the presence of thirteen compounds representing 99.19% of the total constituents. d-Carvone (65.21%) and dl -limonene (27.28%) were identified as the major volatile chemical constituents. Mint oil exhibited promising antioxidant (IC 50 = 26.64 μg/mL) and cytotoxic activity (LC 50 = 245 μg/mL). CLC predicted d-carvone to be active against thyroid gland undifferentiated (anaplastic) carcinoma, pancreatic carcinoma, brain carcinoma, and lymphoblastic leukemia while dl -limonene could be effective against skin melanoma, breast adenocarcinoma in addition to the above carcinomas. Omani spearmint volatile oil exhibited promising cytotoxic and antioxidant activities. However, further detailed studies are warranted to develop mint oil as a natural antioxidant and to unlock its hidden cytotoxic potential. [Display omitted] • Chemical profiling of Omani Mentha spicata species was done by GC-MS analysis. • The GC-MS analysis of mentha volatile oil established it to be a carvone chemotype. • Mentha essential oil exhibited promising antioxidant and cytotoxic activities. • Computational studies revealed carvone and limonene to possess useful bioactivities including cytotoxicity. [ABSTRACT FROM AUTHOR]

This preliminary study was undertaken to evaluate and compare the physicochemical properties, total phenolic content, total flavonoid content and in vitro antioxidant activity of 22 types of monofloral and heterofloral Omani honey. Total phenolic and flavonoid contents were quantified colorimetrically while antioxidant activity was evaluated by 1,1 diphenyl picrylhydrazyl (DPPH) free radical scavenging assay method. Our result clearly shows significant variations among honey samples for all evaluated parameters. Monofloral honey from Salalah, Samail, and Al-Khaboora showed good inhibition of DPPH radicals. The highest amount of total phenol was found in monofloral honey from Al-Dahirah while the highest amount of flavonoid was observed in a monofloral variety from Salalah. A direct relationship between phenol, flavonoid and inhibition of DPPH was also observed. It can be concluded that the monofloral types of honey can be considered particularly useful for human nutrition because of their high phenolic and flavonoid contents which are known for their antioxidant activity. [Display omitted] • Quantification of total phenol and flavonoids of 22 honey samples collected from different regions of Oman. • Free radical scavenging activity of honey samples is reported to predict the nutritional value of honey. • Antibacterial activity of four honey samples is reported. • A comparison of honey samples with respect to refractive index, Brix%, acidity and % of water. [ABSTRACT FROM AUTHOR]

Several generations of antiepileptic drugs (AEDs) are available in the market for the treatment of seizures, but these are amalgamated with acute to chronic side effects. The most common side effects of AEDs are dose-related, but some are idiosyncratic adverse drug reactions (ADRs) that transpire due to the formation of reactive metabolite (RM) after the bioactivation process. Because of the adverse reactions patients usually discontinue the medication in between the treatment. The AEDs such as valproic acid, lamotrigine, phenytoin etc., can be categorized under such types because they form the RM which may prevail with life-threatening adverse effects or immune-mediated reactions. Hepatotoxicity, teratogenicity, cutaneous hypersensitivity, dizziness, addiction, serum sickness reaction, renal calculi, metabolic acidosis are associated with the metabolites of drugs such as arene oxide, N -desmethyldiazepam, 2-(1-hydroxyethyl)-2-methylsuccinimide, 2-(sulphamoy1acetyl)-phenol, E−2-en-VPA and 4-en-VPA and carbamazepine-10,11-epoxide, etc. The major toxicities are associated with the moieties that are either capable of forming RM or the functional groups may itself be too reactive prior to the metabolism. These functional groups or fragment structures are typically known as structural alerts or toxicophores. Therefore, minimizing the bioactivation potential of lead structures in the early phases of drug discovery by a modification to low-risk drug molecules is a priority for the pharmaceutical companies. Additionally, excellent potency and pharmacokinetic (PK) behaviour help in ensuring that appropriate (low dose) candidate drugs progress into the development phase. The current review discusses about RMs in the anticonvulsant drugs along with their mechanism vis -a- vis research efforts that have been taken to minimize the toxic effects of AEDs therapy. [Display omitted] • Reactive metabolites of established antiepileptic drugs (AEDs) with their acute/chronic side-effects are reported. • Various synthetic strategies to minimize the toxicity under each category of AEDs are discussed. • Preclinical data for the synthesized derivatives is represented as compared to standard AEDs. • Structural activity relationship has been discussed for various synthesized derivatives. [ABSTRACT FROM AUTHOR]