Antiproliferative, apoptotic and anti-inflammatory potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues: Novel series of anticancer compounds.

Lung cancer (LC) is the most common cancer in males. As per GLOBOCAN 2020, 8.1 % of deaths and 5.9 % of cases of LC were reported in India. Our laboratory has previously reported the significant anticancer potential of 5H-benzo[h]thiazolo[2,3-b]quinazoline analogues. In this study, we have explored the anticancer potential of 7A {4-(6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazolin-7-yl)phenol} and 9A {7-(4-chlorophenyl)-9-methyl-6,7-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline}by using in-vitro and in-vivo models of LC. In this study, we investigated the antiproliferative potential of quinazoline analogues using A549 cell line to identify the best compound of the series. The in-vitro and molecular docking studies revealed 7A and 9A compounds as potential analogues. We also performed acute toxicity study to determine the dose. After that, in-vivo studies using urethane-induced LC in male albino Wistar rats carried out further physiological, biochemical, and morphological evaluation (SEM and H&E) of the lung tissue. We have also evaluated the antioxidant level, inflammatory, and apoptotic marker expressions. 7A and 9A did not demonstrate any signs of acute toxicity. Animals treated with urethane showed a significant upregulation of oxidative stress. However, treatment with 7A and 9A restored antioxidant markers near-normal levels. SEM and H&E staining of the lung tissue demonstrated recovered architecture after treatment with 7A and 9A. Both analogues significantly restore inflammatory markers to normal level and upregulate the intrinsic apoptosis protein expression in the lung tissue. These experimental findings demonstrated the antiproliferative potential of the synthetic analogues 7A and 9A, potentially due to their anti-inflammatory and apoptotic properties.

Penetrating Sugarcane Injury to Brain via Orbit: A Case Report.

Penetrating brain trauma is rare. We present a unique case involving a sugarcane injury that penetrated the brain via the orbit following a road traffic accident. A 32-year-old male arrived at our emergency department with a penetrating injury to his left eye. A non-contrast computerized tomography (NCCT) scan of the head showed a foreign body in the left orbit, extending to the frontal lobe. Left frontotemporal craniotomy, anterior cranial fossa exploration, retrieval of the foreign body (a sugarcane piece), and dural repair of the anterior cranial fossa were performed. The patient was discharged and showed positive progress on follow-up. Penetrating trauma to the eyes and brain can be fatal, leading to vision loss. Therefore, early surgical intervention and close coordination between ophthalmologists and neurosurgeons are imperative.

From Causatum to Erratum, all in a name.

BACKGROUND: This study highlights how a trivial mistake in collecting timed blood samples of parathyroid hormone (PTH) during parathyroidectomy (PTX) can potentially become a serious error affecting surgical closure. METHODS: For the measurement of serum PTH, the intact PTH (iPTH) test was used to obtain baseline, preoperative, intraoperative, and postoperative samples of PTH, to guide the surgical team regarding adequacy of PTX. RESULTS: Due to the lack of proper guidelines, all types of samples for PTH are labeled as iPTH by the Laboratory Information Services (LIS) software. Due to a human error in marking the PTH vacutainers generated for different time point samples by LIS, samples were swapped. The values in the lab revealed a spurious rise in PTH post-PTX. The laboratory physician carefully observed the tubes and identified the reason for this mistake. The timely action therefore led to surgical closure, otherwise it could have led to unwarranted extended PTX. CONCLUSIONS: In cases where timed samples are mandatory, having a common code for all requisitions can invariably lead to pre-analytical error, therefore proper discriminative measures need to be introduced to avoid these mistakes.

Pre-analytical errors in coagulation testing: a case series.

OBJECTIVES: Prevention of pre-analytical issues in coagulation testing is of paramount importance for good laboratory performance. In addition to common issues like hemolysed, icteric, or lipemic samples, some specific pre-analytical errors of coagulation testing include clotted specimens, improper blood-to-anticoagulant ratio, contamination with other anticoagulants, etc. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are very commonly affected tests due to pre-analytical variables. The impact these parameters possess on surgical decision-making and various life-saving interventions are substantial therefore we cannot afford laxity and casual mistakes in carrying out these critical investigations at all. CASE PRESENTATION: In this case series, a total of 4 cases of unexpectedly deranged coagulation profiles have been described which were reported incorrectly due to the overall casual approach towards these critical investigations. We have also mentioned how the treating clinician and lab physician retrospectively accessed relevant information in the nick of time to bring back reassurance. CONCLUSIONS: Like every other critical investigation, analytical errors can occur in coagulation parameters due to various avoidable pre-analytical variables. The release of spurious results for coagulation parameters sets alarm bells ringing causing much agony to the treating doctor and patient. Only a disciplined and careful approach taken by hospital and lab staff towards each sample regardless of its criticality can negate these stressful errors to a large extent.

Small Intestinal Volvulus Caused by Lipomatosis in a Middle-Aged Female.

Lipomas are benign tumors composed of adipose tissue that can occur in various locations throughout the body, including the gastrointestinal (GI) tract. Lipoma of the small bowel is a rare clinical condition. It infrequently results in small bowel obstruction and volvulus. In most of the patients, it is an incidental diagnosis. However, it may present with abdominal pain, nausea, vomiting, GI bleeding, and constipation. It is commonly diagnosed using imaging studies, such as computerized tomography scan or magnetic resonance imaging. The management of small bowel lipomas depends on the presence of symptoms and the risk of complications. Asymptomatic lipomas can be safely monitored with imaging studies, as the risk of complications is low. However, in symptomatic cases, surgical or endoscopic treatment may be necessary to relieve obstruction and prevent complications. We report a case of volvulus of small bowel in a middle-aged female presenting to our hospital with acute GI symptoms.

Involvement of DPP3 in modulating oncological features and oxidative stress response in esophageal squamous cell carcinoma.

Resistance to therapy in esophageal squamous cell carcinoma (ESCC) is a critical clinical problem and identification of novel therapeutic targets is highly warranted. Dipeptidyl peptidase III (DPP3) is a zinc-dependent aminopeptidase and functions in the terminal stages of the protein turnover. Several studies have reported overexpression and oncogenic functions of DPP3 in numerous malignancies. The present study aimed to determine the expression pattern and functional role of DPP3 in ESCC. DPP3 expression was assessed in normal and tumor tissues using quantitative real-time (qRT)-PCR and corroborated with ESCC gene expression datasets from Gene Expression Omnibus (GEO) and The cancer genome atlas (TCGA). DPP3 stable knockdown was performed in ESCC cells by shRNA and its effect on cell proliferation, migration, cell cycle, apoptosis, and activation of nuclear factor erythroid 2-related factor 2 (NRF2) pathway was assessed. The results suggested that DPP3 is overexpressed in ESCC and its knockdown leads to reduced proliferation, increased apoptosis, and inhibited migration of ESCC cells. Additionally, DPP3 knockdown leads to down-regulation of the NRF2 pathway proteins, such as NRF2, G6PD, and NQO1 along with increased sensitivity toward oxidative stress-induced cell death and chemotherapy. Conclusively, these results demonstrate critical role of DPP3 in ESCC and DPP3/NRF2 axis may serve as an attractive therapeutic target against chemoresistance in this malignancy.

Development and validation of most efficient RNA isolation method from buffalo bull spermatozoa.

BACKGROUND: Being highly fragmented and low in concentration, isolation of good quality RNA from sperm cells is a big challenge. Attempts have been made to evaluate various sperm RNA isolation methods from purified buffalo bull sperm cells. METHODS: Both, non-membrane and membrane-based methods have been evaluated for isolating RNA from Murrah buffalo sperms and compared for their respective efficacies. The traditional TRIzol, TRIzol-heat lysed (H-TRIzol) and cocktail of TCEP-RLT lysis buffer (Qiagen RNeasy mini kit)-TRIzol (C-TRIzol) based isopropanol isolation methods have been evaluated. RESULTS: H-TRIzol yielded best results among conventional methods. The combined T-RLT RNA isolation protocol yielded best quality and quantity compared to other membrane-based methods, due to high lytic property of cocktail of lysis reagents, necessary for complete breakdown of sperm membrane and RNA binding membrane for RNA isolation. Combined lysis performed by treatment with RLT-T and T-RLT differing in order of reagents used were also evaluated. T-RLT combination giving better results compared to RLT-T due to high gDNA contamination and membrane clogging in later protocol steps. CONCLUSION: Overall, in terms of total RNA quantity and quality per million spermatozoa, the heat-lysed TRIzol method (H-TRIzol) performs best among RNA separation techniques employed and is also quite easy to perform. This comparative evaluation of sperm RNA isolation protocols can be useful in deciding the best protocol for isolation of good quality and high concentration sperm RNA from buffalo semen, for transcriptome and other downstream studies.

A facile and green synthesis of Mn and P functionalized graphitic carbon nitride nanosheets for spintronics devices and enhanced photocatalytic performance under visible-light.

Manganese and phosphorus co-doped, graphitic carbon nitride (g-C3N4) nanosheet (Mn/P-g-C3N4) is prepared by facile and green calcination process of melamine (C3H6N6), manganese chloride tetrahydrate (MnCl2·4H2O), and ammonium dihydrogen phosphate ((NH4)H2PO4). The Mn/P co-doping significantly enhances magnetic values compared to pristine-g-C3N4, phosphorus-doped g-C3N4 (P-g-C3N4), and manganese-doped g-C3N4 (Mn-g-C3N4). We find that Mn/P-g-C3N4 is a half-metallic ferromagnetic material having a magnetic moment and Curie temperature of 4.51 µB and âˆ¼ 800 K, respectively. The ultraviolet-visible (UV-vis) absorption spectrum of Mn/P-g-C3N4 reveals superior absorption in broader wavelength compared to pristine-g-C3N4, P-g-C3N4, and Mn-g-C3N4. The methyl orange degradation efficiency of Mn/P-g-C3N4 photocatalyst is 94 %, which is three times more than that of pristine-g-C3N4 (29 %) and more significant than the P-g-C3N4 (46 %) and Mn-g-C3N4 (58 %). Furthermore, density functional theory (DFT) calculation explains the origin of high magnetic behavior, the boosted photocatalytic efficiency of Mn/P-g-C3N4, and the essential material properties like structure, bandgap, the density of states (DOS), and atomic level interaction. This work may be helpful for reasonably designing ferromagnetic material for spintronics devices and boosting visible-light (VL) photocatalytic performance for environmental remediation.

Effect of Curcumin and Coenzyme Q10 Alone and in Combination on Learning and Memory in an Animal Model of Alzheimer's Disease.

The most frequent neurodegenerative illness among senior people and the main cause of dementia is Alzheimer's disease. The present dementia medications available only help with the symptoms of cognitive deficits and have several negative effects. The current study's goal is to assess the effects of curcumin and coenzyme Q10, two herbal medicines, both separately and in combination, on learning and memory before comparing them to the industry standard drug. A total of 42 adult healthy Wistar rats were used in our study. In this experiment, rats were given daily doses of 2.5 mg/kg of body weight of scopolamine hydrobromide for 7 days to induce Alzheimer's disease. On the eighth day, behavioural testing was conducted. Following testing, scopolamine and the test medications were given daily for the following 21 days. On days 29 and 30, behavioural testing was conducted once more, and then animals were slaughtered. Brain homogenate was produced for the estimation of molecular and biochemical markers. Curcumin has demonstrated a dose-response relationship, with a higher dose (200 mg/kg b.w. p.o.) being more effective than a lower dose (100 mg/kg b.w. p.o.). Similar to the greater dose of curcumin, coenzyme Q10 (200 mg/kg b.w. p.o.) has also been found to improve memory and learning. Higher doses of curcumin and coenzyme Q10 had more pronounced and meaningful effects. Acetylcholinesterase and TNF levels increased in scopolamine-induced memory impairment, but these effects were restored by the test medications, and improved by the combined therapy. These outcomes are comparable to those of the common medication memantine. As a result, we may infer from our results that curcumin at higher doses and its combination with coenzyme Q10 (200 mg/kg b.w. p.o.) have a significant impact on cognitive impairment in animal models of Alzheimer's disease and can be utilised alone or as an add-on therapy for the condition.

Identification of stably expressed Internal Control Genes (ICGs) for normalization of expression data in liver of C57BL/6 mice injected with beta casomorphins.

In recent years, beta-casomorphin peptides (BCM7/BCM9) derived from the digestion of cow milk have drawn a lot of attention world over because of their proposed impact on human health. In order to evaluate the transcriptional modulation of target genes through RT-qPCR in response to these peptides, availability of appropriate reference or internal control genes (ICGs) will be the key. The present study was planned to identify a panel of stable ICGs in the liver tissue of C57BL/6 mice injected with BCM7/BCM9 cow milk peptides for 3 weeks. A total of ten candidate genes were evaluated as potential ICGs by assessing their expression stability using software suites; geNorm, NormFinder and BestKeeper. The suitability of the identified ICGs was validated by assessing the relative expression levels of target genes, HP and Cu/Zn SOD. Based on geNorm, PPIA and SDHA gene pair was identified to be most stably expressed in liver tissue during the animal trials. Similarly, NormFinder analysis also identified PPIA as the most stable gene. BestKeeper analysis showed crossing point SD value for all the genes in the acceptable range that is closer to 1. Overall, the study identified a panel of stable ICGs for reliable normalization of target genes expression data in mice liver tissues during BCM7/9 peptides trial.

Demographics and appropriateness of cellular blood component irradiation practices: Ambispective analysis from a tertiary care center.

BACKGROUND: Transfusion-associated graft versus host disease (TA-GVHD) is often underreported. There may also be lapses in TA-GVHD prevention practices due to lack of revision of some of the existing clinical guidelines as well as limited audits on practices of blood component irradiation. This study was undertaken to highlight these shortcomings, and generate data for development of institutional guidelines. METHODS/MATERIALS: Study cohort was selected from patients requiring transfusion support during June 2019 to May 2020. Transfusion history of these patients were followed, both retrospectively and prospectively till July 2021. Transfusion requisitions were categorized as IR (with request for irradiation) or NIR (with no request for irradiation) and justified or unjustified according to published international guidelines. RESULTS: Total 6963 requisitions for cellular blood components were received from 255 patients included in the study cohort. Of these, 3690 (54.9 %) were IR requisitions, while remaining 3029 (45.1 %) requisitions were NIR. Overall, 4242 (63.1 %) requisition were justified for their irradiation status as per published guidelines and 1595 (23.8 %) were found to be Unjustified while justification could not be assessed for remaining 882 (13.1 %) of the requisitions. The highest proportion of Unjustified demands in NIR requisitions was observed in patients with Severe Aplastic anemia (59.4 %). CONCLUSION: Many units were unnecessarily irradiated (7.7 %) while irradiation was missed in 16 % of the requisitions included in analysis which may be attributed to lack of institutional guidelines. We recommend that every centre should adopt a published well-researched guideline including amendments based on review of practices at their center.

Cobalt-catalysed [1,2]-Wittig rearrangement of ethers to secondary alcohols.

Stable ethers are successfully transformed into secondary alcohols via C-O bond activation using a simple cobalt pincer catalyst. Mechanistic studies indicate the involvement of radical pairs, and their sequential recombination and the subsequent hydrolysis results in the formation of secondary alcohols.

Atypical Firearm Injury to the Anterior Triangle of the Neck With an Unusual Projectile Trajectory: A Rare Case Report.

The use of firearms is increasing in our society, which increases the incidence of gunshot injuries in developing countries like India. Gunshot injuries in the neck regions are significantly associated with high mortality and morbidity because of the major vascular and other vital structures present in the neck. However, it's very rare that a bullet may have a trajectory that passes through the neck region and does not damage the vital structures. We present one such case of gunshot injury to the neck. A 20-year-old male reported to the emergency department after sustaining a gunshot wound to the left anterior cervical region of the neck. On examination, the right sternocleidomastoid muscle was taut and tender to the touch. It is very rare that a bullet injury in the neck without damage to even a single vital structure. The most critical steps in managing patients with high-velocity penetrating injuries to the head and neck region are securing an airway, controlling hemorrhage, and identifying and repairing residual traumatic deformities at the earliest possible key points for the best outcome.

Case of mullerian agenesis presenting as bilateral inguinal hernia with left sided irreducibility in a 21 years old female: A rare case report.

INTRODUCTION AND IMPORTANCE: Presence of ovary in an inguinal canal in adult female is a rare presentation. Most of the cases are associated with congenital abnormalities of the female genital tract. The incidence of mullerian agenesis decreases with increasing age. The presence of bilateral inguinal hernia with ovaries as a content in an adult female is extremely rare. CASE PRESENTATION: A 21 year old female presented with bilateral groin swelling with associated pain on left side. On evaluation, there was inguinal hernia on both sides, of which left sided was irreducible. The ultrasonography of groin showed uterus and ovary as contents on left sided sac and ovary on the right side. Considering the severe pain and irreducibility on left side, the exploration of bilateral inguinal regions was done. On exploration, the biopsy was taken and the contents were repositioned back into the pelvis. CLINICAL DISCUSSION: The presence of ovary, uterus or both in the inguinal canal is extremely rare in an adult female. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by normal secondary sexual character with agenesis of uterus and vagina. Karyotype of individual female is essentially 46XX. Early diagnosis is essential to prevent the complications. The primary treatment of irreducible inguinal hernia is exploration and repositioning the contents back to pelvis if grossly normal and repair of inguinal hernia at earliest. CONCLUSION: A case of bilateral inguinal ovarian hernia with irreducibility in an adult female requires an urgent exploration. Delaying the intervention may result in obstruction, strangulation, and subsequent infertility.

Allelic diversity at BoLA DRB3 locus and association with predisposition to clinical mastitis in indicus and crossbred cattle.

Bovine lymphocyte antigen (BoLA) DRB3 locus in healthy and mastitis affected cattle has been genotyped by a polymerase chain reaction and restriction fragment length polymorphisms (PCR-RLFP) using RsaI restriction enzyme, followed by sequencing. In 130 farm animals, 25 BoLA DRB3 alleles have been detected by PCR-RFLP. Three distinct allelic patterns significantly associated with mastitis in Karan Fries crossbred and Sahiwal indicus cattle have been identified, whereas, four other allelic patterns were significantly high in frequency among healthy animals. Sequencing of RFLP genotypes revealed 25 and 47 alleles among healthy Sahiwal and Karan Fries, respectively, while 17 and 38 patterns observed in mastitis affected Sahiwal and Karan Fries animals, respectively. From Tajima's D-test of neutrality, it was concluded that alleles associated with mastitis were expanding in the population, whereas those of healthy were under contraction. Phylogenetic analysis carried out to delineate the evolutionary relationship of the farm and field animals at DRB3 locus, differentiating allelic patterns into six different clusters. Among the phylogenetic lineages, five patterns DRB3*028:01, DRB3*011:03, DRB3*031:01, DRB3*001:01 and DRB3*043:01, were previously reported, whereas one novel allelic variant was observed in indicus and crossbred cattle. This information will help in further exploring the association between BoLA-DRB3 genetic diversity and disease resistance in distinct cattle breeds, important in designing breeding strategies for increasing the distribution of favorable alleles.

Deciphering the nitrate sources and processes in the Ganga river using dual isotopes of nitrate and Bayesian mixing model.

The dual isotopes of dissolved NO3- (n = 43) has been used to delineate the nitrate sources and N-cycling processes in the Ganga river. The proportional contribution of nitrate from different sources has been estimated using the Bayesian mixing model. The seasonal NO3- concentration in the lower stretch of the river Ganga varied between 4.1 and 64.1 µM with higher concentration during monsoon and post-monsoon season and lower concentration during the pre-monsoon and winter season. The temporal variation in the isotopic values ranged between +0.0 and +9.6‰ for δ15NNO3- and -1.2 to +11.0‰ for δ18ONO3-. The spatial NO3- concentration during the post-monsoon season varied between 23.2 and 57.7 µM, with higher values from the middle and lower values from the lower stretch of the river Ganga. The isotopic ratio during the post-monsoon season varied between -1.0 and +11.3‰ for δ15NNO3- and -4.6 to +5.2‰ for δ18ONO3-. The temporal dataset from the lower stretch of the river Ganga showed the dominance of nitrate derived from the nitrification of soil organic matter (SOM) (average ∼53.4%). The nitrate contribution from synthetic fertilizers was observed to be higher during the post-monsoon season (34.7 ± 23.4%) compared to that in the monsoon (25.5 ± 19.5%) and pre-monsoon (22.2 ± 19.6%) season. No significant seasonal variations were observed in the nitrate input from manure/sewage (∼13.9%). Spatial samples collected during the post-monsoon season showed higher contribution of synthetic fertilizer in the lower stretch (34.6 ± 22.7%) compared to the middle stretch (21.1 ± 18.2%), which indicates greater influence of the agricultural activity in the lower stretch. The dual isotope study of dissolved NO3- established that the nitrate in the Ganga river water is mostly derived from the nitrification of incoming organic compounds and is subsequently removed via assimilatory nitrate uptake. The study also emphasises significant nitrification and assimilatory nitrate removal processes operating in the mixing zone of the Ganga river and Hooghly estuary.

Large survey dataset of rice production practices applied by farmers on their largest farm plot during 2018 in India.

This dataset provides detailed information on rice production practices being applied by farmers during 2018 rainy season in India. Data was collected through computer-assisted personal interview of farmers using the digital platform Open Data Kit (ODK). The dataset, n = 8355, covers eight Indian states, viz., Andhra Pradesh, Bihar, Chhattisgarh, Haryana, Odisha, Punjab, Uttar Pradesh and West Bengal. Sampling frames were constructed separately for each district within states and farmers were selected randomly. The survey was deployed in 49 districts with a maximum of 210 interviews per district. The digital survey form was available on mobile phones of trained enumerators and was designed to minimize data entry errors. Each survey captured approximately 225 variables around rice production practices of farmers' largest plot starting with land preparation, establishment method, crop variety and planting time through to crop yield. Detailed modules captured fertilizer application, irrigation, weed management, biotic and abiotic stresses. Additional information was gathered on household demographics and marketing. Geo-points were recorded for each surveyed plot with an accuracy of <10 m. This dataset is generated to bridge a data-gap in the national system and generates information about the adoption of technologies, as well as enabling prediction and other analytics. It can potentially be the basis for evidence-based agriculture programming by policy makers.

Bone Within Bone as a Calcified Subdural Hematoma.

Calcified subdural hematoma (CSDH) is a very rare presentation but a known and reported entity in literature. Most of the case reports have been described in children and the elderly. Surgical treatment for CSDH is still considered controversial. We report here a case of calcified subdural hematoma in a middle-aged male that was successfully operated on. A 45-year-old male presented with complaints of right-sided weakness and seizures with a history of head trauma three years ago. Non-contrast computerized tomography (NCCT) head showed calcified subdural hematoma associated with mass effect and midline shift. A frontotemporoparietal craniotomy was done to remove the CSDH. Intra-operatively the brain was pulsating well. He was discharged on the 12th postoperative day and doing well on a follow-up visit.

Characterization of a xylitol dehydrogenase from Aspergillus flavus and its application in l-xylulose production.

An NAD+-dependent xylitol dehydrogenase from A. flavus (AfXDH) was cloned and successfully expressed in Escherichia coli. AfXDH gene sequence revealed an open reading frame of 1,110 bp, encoding a polypeptide of 369 amino acids with a calculated molecular mass of 38,893 Da. Among various polyols, sorbitol and xylitol were preferred substrates of AfXDH with Km values of 16.2 and 16.9 mM, respectively. AfXDH showed the highest activity in Tris-glycine-NaOH buffer (pH 9.5) at 50°C; it required Zn2+ or Mn2+ for enzyme activity. The half-life at 40°C and half denaturation temperature (T1/2) was 200 min and 45°C, respectively. Bioinformatic analyses along with biochemical properties confirmed that AfXDH belonged to the medium-chain dehydrogenase/reductase family. AfXDH exhibits higher thermostability and k cat values than those of other XDHs. The feasibility of using AfXDH in l-xylulose production was demonstrated. AfXDH, when coupled with Streptococcus pyogenes NADH oxidase, efficiently converted xylitol to l-xylulose with 97% yield, suggesting its usefulness for the industrial l-xylulose production from xylitol.

Systems pharmacology aiding benzimidazole scaffold as potential lead compounds against leishmaniasis for functional therapeutics.

Systems pharmacology helps to understand the complex relationships between biological systems, drugs, and infection model; Leishmania major being one of them. It has aided the drug discovery process by addressing the concerns about economic stress, drug toxicity, and the emergence of resistance. Two million new leishmaniasis cases are reported annually, and >350 million people are at risk globally due to the parasite Leishmania. Trypanothione reductase (TryR) from the parasite-specific redox metabolism is a promising target. In the discipline of medicinal chemistry, benzimidazole is a strong pharmacophore and exhibits a broad range of biological activities. In the current study, benzimidazole derivatives were explored using computational, enzyme kinetics, biological activity, cytotoxic impact characterization, and in-silico ADME-Tox predictions, followed by their confirmation through in-vitro and animal experiments to discover novel inhibitors for TryR from Leishmania major. During rigorous in-silico screening, two benzimidazole derivatives were chosen for further experimentation. In-vitro testing revealed that compound C1 has a higher binding affinity for the TryR protein. Treatment with compound C1 caused significant morphological changes in the parasite, including size reduction, membrane blebbing, loss of motility, and improved anti-leishmanial efficacy. The compound C1 had significant anti-leishmanial potential against L. major promastigotes and demonstrated apoptosis-mediated leishmanicidal activity (apoptosis-like cell death). Furthermore, BALB/c female mice treated with C1 reduced parasite burden. Our findings depicts that C1 successfully lowered the parasite load and has a therapeutic impact on infected mice making C1 as a promising lead compound that, with additional modifications, may be exploited to create novel anti-leishmanial therapies.