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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]

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]