Reusable nano-catalyzed green protocols for the synthesis of quinoxalines: an overview.

Heterocyclic compounds are very widely distributed in nature and are essential for life activities. They play a vital role in the metabolism of all living cells, for example, vitamins and co-enzyme precursors thiamine, riboflavin etc. Quinoxalines are a class of N-heterocycles that are present in a variety of natural and synthetic compounds. The distinct pharmacological activities of quinoxalines have attracted medicinal chemists considerably over the past few decades. Quinoxaline-based compounds possess extensive potential applications as medicinal drugs, presently; more than fifteen drugs are available for the treatment of different diseases. Diverse synthetic protocols have been developed via a one-pot approach using efficient catalysts, reagents, and nano-composites/nanocatalysts etc. But the use of homogeneous and transition metal-based catalysts suffers some demerits such as low atom economy, recovery of catalysts, harsh reaction conditions, extended reaction period, expensive catalysts, the formation of by-products, and unsatisfactory yield of products as well as toxic solvents. These drawbacks have shifted the attention of chemists/researchers to develop green and efficient protocols for synthesizing quinoxaline derivatives. In this context, many efficient methods have been developed for the synthesis of quinoxalines using nanocatalysts or nanostructures. In this review, we have summarized the recent progress (till 2023) in the nano-catalyzed synthesis of quinoxalines using condensation of o-phenylenediamine with diketone/other reagents with plausible mechanistic details. With this review, we hope that some more efficient ways of synthesizing quinoxalines can be developed by synthetic chemists.

A randomised controlled trial comparing two protocols of preoperative antibiotics in patients with positive urine culture undergoing percutaneous nephrolithotomy.

AIM: To compare the outcomes of two different protocols of antibiotic prophylaxis in patients with positive urine culture undergoing percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Patients were prospectively enrolled for the randomised study to either group A which included patients where an attempt to sterilise the urine was made with a 1 week course of sensitive antibiotics or group B that included patients who received a shorter duration of prophylaxis using sensitive antibiotics for 48 h prior to procedure which was continued for 48 h postoperatively. Enrolled patients had stones requiring percutaneous nephrolithotomy and had a positive preoperative urine culture. Primary outcome was difference in sepsis rates between the groups. RESULTS: A total of 80 patients randomised into two groups of 40 each based on the antibiotic protocol used were analysed in the study. There was no difference in infectious complication rates between groups on univariate analysis. The rate of SIRS in Group A and Group B was found to be 20% (N = 8) and 22.5% (N = 9) respectively. The rate of septic shock in Group A and Group B was 7.5% and 5% respectively. On multivariate analysis, longer duration of antibiotics did not decrease the risk of sepsis compared to shorter antibiotic course (p = 0.79). CONCLUSION: Attempts to sterilise urine before PCNL may not decrease the risk of sepsis in patients with positive urine culture undergoing PCNL and may only result in unnecessary prolonging of antibiotic usage thereby increasing the chances of antibiotic resistance.

Imidazopyridine chalcones as potent anticancer agents: Synthesis, single-crystal X-ray, docking, DFT and SAR studies.

New imidazopyridine-chalcone analogs were synthesized through the Claisen-Schmidt condensation reaction. The newly synthesized imidazopyridine-chalcones (S1-S12) were characterized using spectroscopic and elemental analysis. The structures of compounds S2 and S5 were confirmed by X-ray crystallography. The global chemical reactivity descriptor parameter was calculated using theoretically (DFT-B3LYP-3-211, G) estimated highest occupied molecular orbital and lowest unoccupied molecular orbital values and the results are discussed. Compounds S1-S12 were screened on A-549 (lung carcinoma epithelial cells) and MDA-MB-231 (M.D. Anderson-Metastatic Breast 231) cancer cell lines. Compounds S6 and S12 displayed exceptional antiproliferative activity against lung A-549 cancer cells with IC50 values of 4.22 and 6.89 µM, respectively, compared to the standard drug doxorubicin (IC50 = 3.79 µM). In the case of the MDA-MB-231 cell line, S1 and S6 exhibited exceptionally superior antiproliferative activity with IC50 of 5.22 and 6.50 µM, respectively, compared to doxorubicin (IC50 = 5.48 µM). S1 was found to be more active than doxorubicin. Compounds S1-S12 were tested for their cytotoxicity on human embryonic kidney 293 cells, which confirmed the nontoxic nature of the active compounds. Further molecular docking studies verified that compounds S1-S12 have a higher docking score and interacted well with the target protein. The most active compound S1 interacted well with the target protein carbonic anhydrase II in complex with pyrimidine-based inhibitor, and S6 with human Topo IIα ATPase/AMP-PNP. The results suggest that imidazopyridine-chalcone analogs may serve as new leads as anticancer agents.

Long-term renal function in patients undergoing surgical reconstruction for tubercular cicatrized bladder.

PURPOSE: We evaluated the long-term renal function in patients after surgical reconstruction for tuberculous contracted bladder (TBC) and determined factors associated with decreased renal function (RF) during follow up. MATERIALS AND METHODS: We reviewed the records of 61 patients who underwent augmentation cystoplasty (AC) or orthotopic neobladder (ONB) for TBC between June 1994 and August 2019 in our institute. The estimated glomerular filtration rate (eGFR) was calculated preoperatively at initial presentation, before augmentation and at various intervals during follow up. Renal function decrease was defined as a defined as new-onset stage-3A Chronic kidney disease(CKD) or upstaging of pre-operative CKD stage 3A in follow-up. Multivariable analysis was done to evaluate the association of clinicopathological features and postoperative complications with decreased renal function. RESULTS: We analyzed 39 patients who had a minimum follow-up of 1-year post reconstruction. At a median follow-up of 52 months (IQR 31-103 months), 16/39 patients developed RF decrease. In univariate analyses, initial eGFR, and associated ureteric stricture in contralateral renal unit were significantly associated with new-onset renal insufficiency (p < 0.001 each). On multivariable analysis, only initial presenting eGFR (p < 0.001) was an independent predictor of new-onset renal insufficiency. ROC cut-off levels for eGFR at presentation predicting the primary end point of RF decrease was 45 ml/min. CONCLUSIONS: Decreased renal function is noted in most patients during long term follow-up after surgical reconstruction for TBC. After controlling for preoperative and postoperative risk factors, patients with initial presenting GFR < 45 ml/min are at greater risk of a decline in renal function following reconstruction.

Development and Characterization of Pullulan-Based Orodispersible Films of Iron.

Iron deficiency is the principal cause of nutritional anemia and it constitutes a major health problem, especially during pregnancy. Despite the availability of various non-invasive traditional oral dosage forms such as tablets, capsules, and liquid preparations of iron, they are hard to consume for special populations such as pregnant women, pediatric, and geriatric patients with dysphagia and vomiting tendency. The objective of the present study was to develop and characterize pullulan-based iron-loaded orodispersible films (i-ODFs). Microparticles of iron were formulated by a microencapsulation technique, to mask the bitter taste of iron, and ODFs were fabricated by a modified solvent casting method. Morphological characteristics of the microparticles were identified by optical microscopy and the percentage of iron loading was evaluated by inductively coupled plasma optical emission spectroscopy (ICP-OES). The fabricated i-ODFs were evaluated for their morphology by scanning electron microscopy. Other parameters including thickness, folding endurance, tensile strength, weight variation, disintegration time, percentage moisture loss, surface pH, and in vivo animal safety were evaluated. Lastly, stability studies were carried out at a temperature of 25 °C/60% RH. The results of the study confirmed that pullulan-based i-ODFs had good physicochemical properties, excellent disintegration time, and optimal stability at specified storage conditions. Most importantly, the i-ODFs were free from irritation when administered to the tongue as confirmed by the hamster cheek pouch model and surface pH determination. Collectively, the present study suggests that the film-forming agent, pullulan, could be successfully employed on a lab scale to formulate orodispersible films of iron. In addition, i-ODFs can be processed easily on a large scale for commercial use.

Catalytic role in Biginelli reaction: Synthesis and biological property studies of 2-oxo/thioxo-1,2,3,4-tetrahydropyrimidines.

The Biginelli reaction has received significant consideration in recent years due to its easily accessible aldehyde, urea/thiourea, and active methylene compounds. When it comes to pharmacological applications, the Biginelli reaction end-products, the 2-oxo-1,2,3,4-tetrahydropyrimidines, are vital in pharmacological applications. Due to the ease of carrying out the Biginelli reaction, it offers a number of exciting prospects in various fields. Catalysts, however, play an essential role in Biginelli's reaction. In the absence of a catalyst, it is difficult to form products with a good yield. Many catalysts have been used in search of efficientmethodologies, including biocatalysts, Brønsted/Lewis acids, heterogeneous catalysts, organocatalysts, and so on. Nanocatalysts are currently being applied in the Biginelli reaction to improve the environmental profile as well as speed up the reaction process. This review describes the catalytic role in the Biginelli reaction and pharmacological application of 2-oxo/thioxo-1,2,3,4-tetrahydropyrimidines. This study provides information that will facilitate the development of newer catalytic methods for the Biginelli reaction, by academics as well as industrialists. It also offers a broad scope for drug design strategies, which may enable the development of novel and highly effective bioactive molecules.

Design, synthesis, molecular docking, and biological evaluation of coumarin-thymidine analogs as potent anti-TB agents.

With the intent to discover new antituberculosis (TB) compounds, coumarin-thymidine analogs were synthesized using second-order nucleophilic substitution reactions of bromomethyl coumarin with thymidine. The newly synthesized coumarin-thymidine conjugates (1a-l) were characterized using IR, NMR, GC-MS, and CHN elemental analysis. The novel conjugates were found to exhibit potent anti-TB activity against the Mycobacterium tuberculosis H37 Rv strain, with minimum inhibitory concentrations (MIC) of the active compounds ranging between 0.012 and 0.482 µM. Compound 1k was established as the most active candidate with a MIC of 0.012 µM. The toxicity study on HEK cells confirmed the nontoxic nature of compounds 1e, 1h, 1i, 1j, and 1k. Also, the most active compounds (1k, 1j, and 1e) were stable in the pH range from 2.5 to 10, indicating compatibility with the biophysical environment. Based on the pKa studies, compounds 1k, 1j, and 1e are capable of crossing lipid-membrane barriers and acting on target cells. Molecular docking studies on the M. tuberculosis ß-oxidation trifunctional enzyme (PDB ID: 7O4V) were conducted to investigate the mechanisms of anti-TB activity. All compounds showed excellent hydrogen binding interactions and exceptional docking scores against M. tuberculosis, which was in accordance with the results. Compounds 1a-l possessed excellent affinity to proteins, with binding energies ranging from -7.4 to -8.7 kcal/mol.

Dual functions: A coumarin-chalcone conjugate inhibits cyclic-di-GMP and quorum-sensing signaling to reduce biofilm formation and virulence of pathogens.

Antibiotic resistance or tolerance of pathogens is one of the most serious global public health threats. Bacteria in biofilms show extreme tolerance to almost all antibiotic classes. Thus, use of antibiofilm drugs without bacterial-killing effects is one of the strategies to combat antibiotic tolerance. In this study, we discovered a coumarin-chalcone conjugate C9, which can inhibit the biofilm formation of three common pathogens that cause nosocomial infections, namely, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli, with the best antibiofilm activity against P. aeruginosa. Further investigations indicate that C9 decreases the synthesis of the key biofilm matrix exopolysaccharide Psl and bacterial second messenger cyclic-di-GMP. Meanwhile, C9 can interfere with the regulation of the quorum sensing (QS) system to reduce the virulence of P. aeruginosa. C9 treatment enhances the sensitivity of biofilm to several antibiotics and reduces the survival rate of P. aeruginosa under starvation or oxidative stress conditions, indicating its excellent potential for use as an antibiofilm-forming and anti-QS drug.

ON donor tethered copper (II) and vanadium (V) complexes as efficacious anti-TB and anti-fungal agents with spectroscopic approached HSA interactions.

Antimicrobial drug resistance poses a significant threat worldwide, hence triggering an urgent situation for developing feasible drugs. 3D-transition metal coordination complexes being multifaceted, offer tremendous potency as drug candidates. However, there are fewer reports on non-toxic and safe transition metal complexes; therefore, we hereby attempted to develop novel copper and vanadium-based therapeutic agents. We have synthesised six metal complexes viz., [VVO2(Quibal-INH)] (1), [CuII(Quibal-INH)2] (2), [VVO(Quibal-INH) (cat)] (3), [CuII(Quibal-INH) (cat)] (4), [VVO(Quibal-INH) (bha)] (5) and [CuII(Quibal-INH) (bha)] (6). Quibal-INH (L) is an ON bidentate donor ligand synthesized from Schiff base reaction between 4-(2-(7-chloroquinolin-3-yl)vinyl)benzaldehyde (Quibal) and Isoniazid (INH). The synthesized compounds were characterized using analytical techniques involving ATR-IR, UV-Vis, EPR, 1H NMR, 13C NMR, and 51V NMR. Ligand (L) and compound 3 exhibited moderate growth inhibitory activity towards Candida albicans and Cryptococcus neoformans fungal species. Compound 6 has been identified as active against the above fungal species with no toxicity and hemolysis activity on the healthy cells. Compound 5 exhibited significant activity against the Mycobacterium tuberculosis H 37 R v strain. Further, compounds 4, 5 and 6 exhibited excellent free radical scavenging activity. All the developed compounds were found to exhibit stability over a wide range of pH conditions. The complexes were additionally studied for their interaction with human serum albumin (HSA) with the UV-vis spectroscopic technique.

Drug re-engineering and repurposing: A significant and rapid approach to tuberculosis drug discovery.

The prevalence of tuberculosis (TB) remains the leading cause of death from a single infectious agent, ranking it above all other contagious diseases. The problem to tackle this disease seems to become even worse due to the outbreak of SARS-CoV-2. Further, the complications related to drug-resistant TB, prolonged treatment regimens, and synergy between TB and HIV are significant drawbacks. There are several drugs to treat TB, but there is still no rapid and accurate treatment available. Intensive research is, therefore, necessary to discover newer molecular analogs that can probably eliminate this disease within a short span. An increase in efficacy can be achieved through re-engineering old TB-drug families and repurposing known drugs. These two approaches have led to the production of newer classes of compounds with novel mechanisms to treat multidrug-resistant strains. With respect to this context, we discuss structural aspects of developing new anti-TB drugs as well as examine advances in TB drug discovery. It was found that the fluoroquinolone, oxazolidinone, and nitroimidazole classes of compounds have greater potential to be further explored for TB drug development. Most of the TB drug candidates in the clinical phase are modified versions of these classes of compounds. Therefore, here we anticipate that modification or repurposing of these classes of compounds has a higher probability to reach the clinical phase of drug development. The information provided will pave the way for researchers to design and identify newer molecular analogs for TB drug development and also broaden the scope of exploring future-generation potent, yet safer anti-TB drugs.

An interesting presentation of invasive bladder carcinoma as pseudo renal failure / Uma apresentação interessante do carcinoma invasivo de bexiga como pseudo insuficiência renal

Abstract Ascites and oliguria with an increasing serum creatinine level are often observed in patients with acute renal failure. However, these symptoms are also noted in individuals with intraperitoneal urinary leakage and can be mistaken for acute renal failure. This rise in creatinine in such patients is called pseudo renal failure and it happens by a process of reverse peritoneal dialysis. In literature, the most commonly described condition that leads to this clinical picture is following a spontaneous or missed bladder perforation. We, herein, report a case of carcinoma of the bladder that presented with features resembling acute renal failure, which later turned out to be pseudo renal failure due to intraperitoneal urinary extravasation from a forniceal rupture. The patient was managed with emergency with a percutaneous drain followed by a percutaneous nephrostomy, which led to normalization of creatinine. Cystoscopy revealed the bladder growth in an intact small capacity bladder and biopsy confirmed it as a muscle invasive squamous cell carcinoma. Due to advanced nature of his malignancy, he underwent a palliative ileal conduit diversion but he later developed chest metastasis and ultimately succumbed to the disease. Intraperitoneal urinary leakage due to forniceal rupture presenting as pseudo renal failure is a rare presentation of carcinoma bladder. Sudden onset abdominal discomfort, increasing ascites, hematuria, and oliguria with elevated renal parameters needs consideration and exclusion of this entity. The diagnostic dilemma associated with this rare presentation along with the management and prognosis in such patients of carcinoma bladder are discussed.

Resumo Ascite e oligúria com um nível crescente de creatinina sérica são frequentemente observadas em pacientes com insuficiência renal aguda. Entretanto, esses sintomas também são notados em indivíduos com extravasamento urinário intraperitoneal e podem ser diagnosticados como lesão renal aguda erroneamente. Este aumento de creatinina em tais pacientes é chamado de pseudo insuficiência renal e ocorre por um processo de diálise peritoneal reversa. Na literatura, a condição mais comumente descrita que leva a este quadro clínico se dá após uma perfuração vesical espontânea ou perdida. Relatamos aqui um caso de carcinoma de bexiga que apresentou características semelhantes à insuficiência renal aguda, e mais tarde se revelou uma pseudo insuficiência renal devido a extravasamento urinário intraperitoneal de uma ruptura de fórnice renal. O paciente foi tratado com emergência com um dreno percutâneo seguido por uma nefrostomia percutânea, que levou à normalização da creatinina. A cistoscopia revelou o crescimento da bexiga em uma bexiga intacta, de pequena capacidade e que a biópsia confirmou como um carcinoma escamoso invasivo muscular. Devido à natureza avançada de sua malignidade, ele foi submetido a um desvio de conduto ileal paliativo, mas posteriormente desenvolveu metástase torácica e acabou sucumbindo à doença. O vazamento urinário intraperitoneal devido à ruptura do fórnice renal que se apresenta como pseudo insuficiência renal é uma apresentação rara do carcinoma vesical. Desconforto abdominal de início súbito, ascite crescente, hematúria e oligúria com elevados parâmetros renais precisam de consideração e exclusão desta entidade. O dilema diagnóstico associado a esta rara apresentação, juntamente com o controle e prognóstico em tais pacientes de carcinoma vesicular, são discutidos.

An interesting presentation of invasive bladder carcinoma as pseudo renal failure.

Ascites and oliguria with an increasing serum creatinine level are often observed in patients with acute renal failure. However, these symptoms are also noted in individuals with intraperitoneal urinary leakage and can be mistaken for acute renal failure. This rise in creatinine in such patients is called pseudo renal failure and it happens by a process of reverse peritoneal dialysis. In literature, the most commonly described condition that leads to this clinical picture is following a spontaneous or missed bladder perforation. We, herein, report a case of carcinoma of the bladder that presented with features resembling acute renal failure, which later turned out to be pseudo renal failure due to intraperitoneal urinary extravasation from a forniceal rupture. The patient was managed with emergency with a percutaneous drain followed by a percutaneous nephrostomy, which led to normalization of creatinine. Cystoscopy revealed the bladder growth in an intact small capacity bladder and biopsy confirmed it as a muscle invasive squamous cell carcinoma. Due to advanced nature of his malignancy, he underwent a palliative ileal conduit diversion but he later developed chest metastasis and ultimately succumbed to the disease. Intraperitoneal urinary leakage due to forniceal rupture presenting as pseudo renal failure is a rare presentation of carcinoma bladder. Sudden onset abdominal discomfort, increasing ascites, hematuria, and oliguria with elevated renal parameters needs consideration and exclusion of this entity. The diagnostic dilemma associated with this rare presentation along with the management and prognosis in such patients of carcinoma bladder are discussed.

Locked-In Syndrome: A Systematic Review of Long-Term Management and Prognosis.

Locked-in syndrome (LIS) is a neurological disorder in which there is damage to the ventral pons and caudal midbrain. An ischemic cause, such as basilar artery occlusion, can often lead to LIS. LIS has three subtypes: classical, partial, and total. There is loss of motion in the four extremities in classical LIS, loss of horizontal gaze, and aphasia. In partial LIS, the patient still has some motor function. Complete LIS has the worst outcome because patients cannot blink or have vertical gaze, thus rendering them incapable of communicating. Most cases of LIS occur due to ischemic infarcts. These patients require a great deal of physical rehabilitation to regain partial motor ability and a means to communicate. While the clinical features and pathophysiology are known, the prognosis and long-term treatment remain unknown. We conducted a systematic review using the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) protocol. We use an advanced PubMed strategy using the inclusion criteria of observational studies or clinical trials conducted in the last 20 years, written in English, and conducted on humans. We excluded systematic reviews, literature reviews, metanalysis, and studies that did not meet the outcomes of our objectives. The prognosis of LIS is not good, and most patients remain locked in, with poor quality of life, especially motor functions. Respiratory failure and depression are big comorbidities. In the acute setting, patients benefit from rapid intervention. The subacute treatment needs to manage aggressively to improve functional scores best. The long-term treatment focus is on the quality of life and managing comorbidities.

Posterior urethral mini-valves causing urinary tract infection: A report of 3 cases.

Posterior urethral valves have myriad presentations based on the severity of obstruction with the milder end of spectrum often termed as mini-valves. The simultaneous occurrence of ureteropelvic junction obstruction and urethral valves has not been described before and is most likely coincidental. Herein, we discuss the management of three boys who had febrile urinary tract infection following pyeloplasty and on evaluation were found to have valves. This article highlights the need for considering these mini-valves as a possibility in boys presenting with symptoms following pyeloplasty so as to avoid delay in diagnosis and unnecessary morbidity in these children.

Efficacy and Toxicity of Fexinidazole and Nifurtimox Plus Eflornithine in the Treatment of African Trypanosomiasis: A Systematic Review.

Human African trypanosomiasis (HAT), or sleeping sickness disease, is an infection caused mainly by Trypanosoma brucei gambiense-human African trypanosomiasis (g-HAT) and is transmitted by tsetse flies. The disease goes through two stages: hemolymphatic and meningo-encephalic phases. The treatment for the second stage has changed from melarsoprol or eflornithine to nifurtimox-eflornithine combination therapy (NECT) and fexinidazole. We aimed to systematically review the literature on the efficacy and toxicity of fexinidazole and NECT. We used PubMed advanced strategy and Google Scholar databases, including clinical trials and observational studies on humans in the last 20 years in the English literature. Applying the inclusion/exclusion criteria, we reviewed eight studies. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol. For assessing bias, we used the Cochrane Collaboration's tool for risk assessment of the clinical trials and the Robins-I tool for the observational studies. Overall, the clinical trials showed that NECT was non-inferior to eflornithine. The proportion of patients discharged alive is higher in patients treated with NECT vs. patients treated with eflornithine. Gastrointestinal complaints are a common side effect of NECT therapy, while fearful but relatively rare convulsions can also occur. The main limitation among the studies of NECT was the lack of blinding because most of them were open-label. Fexinidazole, the new oral medication showed is effective and safe for the treatment of g-HAT infection. Because of their convenience, fexinidazole is preferred over NECT therapy, oral vs. IV infusion in the first and second stages of the disease. Compared to older therapies, fexinidazole and NECT are more effective and safer than eflornithine and melarsoprol monotherapy.

Presentation, management and outcomes of pediatric urogenital tuberculosis: 20 years' experience from a tertiary center.

BACKGROUND: Urogenital tuberculosis (UGTB) has traditionally being a diagnosis of adulthood and is supposed to be rare in children, as it is believed that the symptoms of renal tuberculosis do not appear for 10 or more years after the primary infection. While this may be true in developed countries, where childhood pulmonary tuberculosis is a rarity nowadays. In developing countries, childhood pulmonary tuberculosis is still a major issue and hence, UGTB is not an uncommon diagnosis in younger children and adolescents in these countries. Considering this dearth of data on childhood UGTB, we retrospectively evaluated our series of children with this disease, with special emphasis on the role of surgery. OBJECTIVE: To analyze the clinical presentation, management strategies and outcomes of pediatric UGTB managed in a tertiary care center. MATERIALS AND METHODS: Case records of children and adolescents ≤18 years diagnosed with UGTB during the period July 1998 to June 2018 at our center were reviewed. Clinical features, organ involvement, investigations, treatment and outcome of therapy were studied. RESULTS: There were 41 children and adolescents (M: F = 22:19) identified, with a mean age of 14.8 ± 3.9 years who fulfilled the inclusion criteria. The most common presentation was flank pain and irritative storage symptoms. Mycobacterium tuberculosis was identified on urinary examination in only 17 (41.5%) cases. Six patients were lost to follow up after initial diagnosis. A total of 45 procedures (35 primary and 10 secondary) were performed in 35 children. Initial diversion in the form of PCN and DJS were done in 11 and 12 patients respectively, of which 8 were managed with stenting alone. Surgical management was done mostly in the form of nephrectomy (15), nephrectomy along with reconstruction (5) and reconstruction only (6). On univariate analysis, factors associated with nephrectomy were poor initial function and nephrostomy as initial diversion. Overall median follow-up was 25 (IQR 15.5-74.25) months. During follow up, chronic renal failure developed in nearly 53.8% of patients who underwent major reconstruction. CONCLUSIONS: Urogenital tuberculosis presents with a wide spectrum of clinical features and pathological lesions. Diagnosis is often delayed because of late presentation and many children present with cicatrization sequelae. Antitubercular drug therapy and judicious application of minimally invasive diversions and surgery (both ablative and reconstructive) achieve satisfactory results in the majority of cases. Children undergoing major surgical reconstruction in particular need to be followed up rigorously and counselled about possibility of development of renal failure.

Coumarin hybrid derivatives as promising leads to treat tuberculosis: Recent developments and critical aspects of structural design to exhibit anti-tubercular activity.

Tuberculosis (TB) is a highly contagious airborne disease with nearly 25% of the world's population infected with it. Challenges such as multi drug resistant TB (MDR-TB), extensive drug resistant TB (XDR-TB) and in rare cases totally drug resistant TB (TDR-TB) emphasizes the critical and urgent need in developing novel TB drugs. Moreover, the prolonged and multi drug treatment regime suffers a major drawback due to high toxicity and vulnerability in TB patients. This calls for intensified research efforts in identifying novel molecular scaffolds which can combat these issues with minimal side effects. In this pursuit, researchers have screened many bio-active molecules among which coumarin have been identified as promising candidates for TB drug discovery and development. Coumarins are naturally occurring compounds known for their low toxicity and varied biological activity. The biological spectrum of coumarin has intrigued medicinal researchers to investigate coumarin scaffolds for their relevance as anti-TB drugs. In this review we focus on the recent developments of coumarin and its critical aspects of structural design required to exhibit anti-tubercular (anti-TB) activity. The information provided will help medicinal chemists to design and identify newer molecular analogs for TB treatment and also broadens the scope of exploring future generation potent yet safer coumarin based anti-TB agents.

Biscoumarin-pyrimidine conjugates as potent anticancer agents and binding mechanism of hit candidate with human serum albumin.

In our continuing efforts to develop therapeutically active coumarin-based compounds, a series of new C4-C4' biscoumarin-pyrimidine conjugates (1a-l) was synthesized via SN 2 reaction of substituted 4-bromomethyl coumarin with thymine. All compounds were characterized using spectroscopic techniques, that is, attenuated total reflection infrared (ATR-IR), CHN elemental analysis, and 1 H and 13 C NMR (nuclear magnetic resonance). In addition, the structure of compound 1d (1,3-bis[(7-chloro-2-oxo-2H-chromen-4-yl)methyl]-5-methylpyrimidine-2,4(1H,3H)-dione) was established through X-ray crystallography. Compounds 1a-l were screened for in vitro anticancer activity against C6 rat glioma cells. Among the screened compounds, 1,3-bis[(6-chloro-2-oxo-2H-chromen-4-yl)methyl]-5-methylpyrimidine-2,4(1H,3H)-dione (1c) was identified as the best antiproliferative candidate, exhibiting an IC50 value of 4.85 µM. All the compounds (1a-l) were found to be nontoxic toward healthy human embryonic kidney cells (HEK293), indicating their selective nature. In addition, the most active compound (1c) displayed strong binding interactions with the drug carrier protein, human serum albumin, and exhibited good solution stability at biological pH conditions. Fluorescence, UV-visible spectrophotometry and molecular modeling methodologies were employed for studying the interaction mechanism of compound 1c with protein.