Development, validation and a GAPI greenness assessment for the determination of 103 pesticides in mango fruit drink using LC-MS/MS.

A robust method was developed using LC-ESI-MS/MS-based identification and quantification of 103 fortified pesticides in a mango fruit drink. Variations in QuEChERS extraction (without buffer, citrate, and/or acetate buffered) coupled with dispersive clean-up combinations were evaluated. Results showed 5 mL dilution and citrate buffered QuEChERS extraction with anhydrous (anhy) MgSO4 clean-up gave acceptable recovery for 100 pesticides @ 1 µg mL-1 fortification. The method was validated as per SANTE guidelines (SANTE/11813/2021). 95, 91, and 77 pesticides were satisfactorily recovered at 0.1, 0.05, and 0.01 µg mL-1 fortification with HorRat values ranging from 0.2-0.8 for the majority. The method showed matrix enhancement for 77 pesticides with a global uncertainty of 4.72%-23.89%. The reliability of the method was confirmed by real sample analysis of different brands of mango drinks available in the market. The greenness assessment by GAPI (Green Analytical Procedure Index) indicated the method was much greener than other contemporary methods.

Comparison of Gastric Insufflation Volume Between Ambu AuraGain and ProSeal Laryngeal Mask Airway Using Ultrasonography in Patients Undergoing General Anesthesia: A Randomized Controlled Trial.

INTRODUCTION: Ambu AuraGain and ProSeal laryngeal mask airway are second-generation supraglottic airway devices (SADs) with added advantage of gastric drain and better oropharyngeal sealing pressure. The primary objective was to study the difference in the gastric insufflation volume between Ambu AuraGain and ProSeal LMA in patients undergoing general anesthesia. METHODS: This randomized controlled trial involving 120 adult patients scheduled under general anesthesia were randomized into either Ambu AuraGain or LMA ProSeal group. Gastric cross-sectional area was measured using ultrasonography at baseline, after mask ventilation, and at the end of surgery. Gastric volume was calculated from the measured cross-sectional area. Oropharyngeal sealing pressure, peak airway pressure, and postoperative complications were noted. Statistical analysis was done using SPSS version 22 (Armonk, NY: IBM Corp.) and p < 0.05 was considered statistically significant. RESULTS: Demographic profile of the study groups was comparable. There was a significant difference in gastric volume between the groups at the end of surgery with 5.91 ml (±9.68 ml) in Ambu AuraGain group and 12.28 ml (±13.05 ml) in the LMA ProSeal group (p = 0.001). Similarly, there was a difference in volume between baseline and at the end of the surgery within the groups also (Ambu AuraGain group, p=0.0012; LMA ProSeal group, p=0.0015, respectively). Though the oropharyngeal sealing pressure and peak airway pressures were comparable, increased incidence of postoperative complications was observed with LMA ProSeal. CONCLUSION: Thus, Ambu AuraGain resulted in a lower gastric insufflation volume than LMA ProSeal with lesser incidence of postoperative complications.

Preoperative Vascular Function Assessment and Perioperative Vascular Events in Patients Posted for Elective Non-cardiac Surgeries.

Background Coronary atherosclerosis is usually asymptomatic until a major cardiac event occurs. Surgery is one of the major stress factors that play a role in hastening vascular deterioration in susceptible patients. Non-invasive tests to detect atherosclerosis and endothelial dysfunction have started gaining popularity nowadays, and of the several options, carotid artery intima-media thickness (IMT) and radial artery flow-mediated dilation (FMD) are two promising tests for detecting cardiovascular impairment. Methods This was a pilot study that was undertaken on 100 patients in a tertiary care medical center (Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry) between June 2015 and August 2016 with the aim of studying the prevalence of endothelial dysfunction and early atherosclerosis in the given population, and to find out the predictive power of preoperative vascular functional assessment in the prediction of perioperative cardiovascular events in the same population. We had selected patients who had at least two risk factors for endothelial dysfunction and were posted for elective non-cardiac surgical procedures via convenience sampling. Flow-mediated vasodilatation of the radial artery (FMD) and carotid intima-media thickness (CIMT) were measured on the previous day of surgery, while a fasting lipid profile was collected from the patients on the morning of the surgery. Endothelial dysfunction was defined as FMD<4.5%, while atherosclerosis was defined as CIMT>0.07 cm. Demographic details and baseline hemodynamic parameters of the patients were also noted preoperatively as well as intra-operatively, and patients were followed up for any major clinical adverse cardiovascular event post-operatively till they were discharged from the hospital. Results It was found that the prevalence of endothelial dysfunction was 23%, while the prevalence of early atherosclerosis was 33% in our study population. However, it was found that FMD and CIMT did not correlate with each other significantly, nor did they correlate significantly with perioperative cardiovascular events. The risk factors of the patients also did not correlate with the FMD and CIMT values of the patients in which they were impaired. Moreover, they did not have any significant correlation with the perioperative events that occurred. Conclusion The prevalence of endothelial dysfunction in our tertiary center was found to be 23%, and the prevalence of atherosclerosis was 33% in patients posted for elective non-cardiac surgery who had multiple risk factors. It was also found that non-invasive preoperative vascular assessment was not quite effective as hypothesized in predicting perioperative cardiovascular events.

Heteroaryl ether analogues of an antileishmanial 7-substituted 2-nitroimidazooxazine lead afford attenuated hERG risk: In vitro and in vivo appraisal.

Previous investigation of the potent antileishmanial properties of antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines with biaryl side chains led to our development of a new clinical candidate for visceral leishmaniasis (DNDI-0690). Within a collaborative backup program, a racemic monoaryl lead (3) possessing comparable activity in mice but a greater hERG liability formed the starting point for our pursuit of efficacious second generation analogues having good solubility and safety. Asymmetric synthesis and appraisal of its enantiomers first established that chiral preferences for in vivo efficacy were species dependent and that neither form afforded a reduced hERG risk. However, in line with our findings in a structurally related series, less lipophilic heteroaryl ethers provided significant solubility enhancements (up to 16-fold) and concomitantly attenuated hERG inhibition. One promising pyridine derivative (49) displayed 100% oral bioavailability in mice and delivered a 96% parasite burden reduction when dosed at 50 mg/kg in a Leishmania donovani mouse model of visceral leishmaniasis.

Psychomotor recovery of dexmedetomidine compared with propofol after sedation during spinal anesthesia: A randomized control trial.

BACKGROUND AND AIMS: Early psychomotor recovery is an essential part of day care surgery which depends on brain integration of motor and sensory co-ordination. Even though dexmedetomidine is commonly used for day care procedures, the recovery profile was not studied. Hence, this study was designed to evaluate the psychomotor recovery of sedation with dexmedetomidine during spinal anesthesia. MATERIAL AND METHODS: Sixty-six patients were included. Group D received dexmedetomidine 0.5 µg/kg (loading dose) followed by 0.2-1 µg/kg/hour. Group P received propofol infusion of 25-100 µg/kg/minute. Psychomotor recovery was assessed by finger-tapping, manual dexterity, visual spatial memory capacity, and pen and paper tests. Psychomotor tasks were given to the patients postoperatively at every 30 minutes for 2 hours followed by every hour up to 4 hours after surgery. Distribution of patients, age, weight, duration of surgery, and the level of sensory blockade was compared using independent t-test. Student's t-test has been used to find the significance of parameters such as heart rate, mean arterial pressure, oxygen saturation (SpO2), psychomotor recovery between two groups. P < 0.05 was considered as significant. RESULTS: The motor recovery using finger tapping test was faster in Group D than Group P (73.94 ± 42.13 vs 101.21 ± 37.98 minutes, P-value = 0.007). Motor recovery using peg board test was faster in Group P than Group D (82.12 ± 40.37 vs 99.39 ± 43.08 minutes, P-value = 0.098). Visual spatial capacity memory test and pen and paper test were unaffected. CONCLUSIONS: We conclude that patients who received dexmedetomidine showed earlier recovery with finger tapping test. Hence, we suggest to use dexmedetomidine for complete psychomotor recovery and fast-track discharging of the patient after spinal anesthesia.

Effect of immobilised cervical spine on oropharyngeal sealing pressure with Ambu AuraGain™ Supraglottic airway: A randomised crossover trial.

BACKGROUND AND AIMS: Ambu® AuraGain™ laryngeal airway (AuraGain) is one of the newer supraglottic airway device introduced in 2014. Cervical spine stabilisation with hard cervical collar makes insertion of supraglottic airways and tracheal intubation difficult. This study was conducted to investigate whether the presence of a cervical collar affects the oropharyngeal sealing pressure (OSP) and fibreoptic view of the glottis (Brimacombe score) in airways secured with the AuraGain. METHODS: The study was a randomised crossover trial. Thirty five ASA 1-3 patients undergoing elective surgery under general anaesthesia were recruited for the study. In each patient AuraGain was inserted twice in a crossover manner once with and once without a hard cervical collar in situ, with the sequence of insertion randomised. During each insertion of AuraGain the OSP, fibreoptic view of the glottis, insertion parameters, ventilator data and complications were noted. RESULTS: The mean OSPs in both the groups were similar with no significant difference (29.6 ± 3.7 cmH2O without collar and 30.1 ± 3.1 cmH2O with collar [P = 0.310]). The fibreoptic view of glottis was also similar in both groups. The insertion with collar was more difficult than without collar. The number of attempts for successful insertion was same in both the groups. The time taken for appropriate placement of LMA was significantly prolonged in patients with collar. CONCLUSIONS: We conclude that the Ambu AuraGain can be used to provide effective ventilation in patients whose cervical spine is immobilised with a hard cervical collar.

Evaluation of Neurosensory Function Following Inferior Alveolar Nerve Lateralization for Implant Placement.

BACKGROUND: Adequate bone height and width is the most important parameter for success of implants. Prolonged edentulous area in mandibular posterior region is often associated with atrophy precluding the use of dental implants. Inferior alveolar nerve (IAN) lateralization is a challenging surgical procedure as it involves the exposure of the neurovascular bundle from its compact bony compartment and adequate retraction while immediate placement of implant. AIM: Evaluation of neurosensory disturbances related to IAN lateralization for implant placement in the posterior atrophic edentulous mandible. MATERIALS AND METHODS: Ten patients above the age of 18 years with an edentulous span in mandibular posterior region showing distance from alveolar crest to IAN ≤ 8 mm (CBCT) were included in the study. The postoperative analysis of NDs was done using Semmes-Weinstein Monofilaments (SWM). Readings were made on the 1st and 7th postoperative day and every month thereafter until the neural sensations were restored. RESULTS: All patients reported neurosensory disturbance on post-op day 1. None of the patients responded to SWM lesser than 4.56 on first postoperative day, which indicated 100% incidence of neurosensory disturbances. The minimum time required for complete recovery was 2.0 months, and maximum was 4.0 months. CONCLUSION: IAN lateralization is a useful method for managing the atrophic posterior mandible with dental implants. If done precisely with experienced personnel, it can provide a worthy option for surgical restoration of atrophic mandible with minimal temporary NDs.

gem-Dithioacetylated indole derivatives as novel antileishmanial agents.

In this communication we report a serendipitously discovered hybrid molecule 1, combining fragment of 3 (an in vivo active antileishmanial molecule) with H2S donor moiety (known for bimodal behavior of cytoprotection and apoptosis), as antileishmanial agent. Compound 1 suppresses 99.82% parasitemia of L. donovani infected macrophages at 12.5µg/ml without even deforming them (CC50>100µg/ml). This compound appears cytotoxic for intracellular amastigotes while cytoprotective to host macrophages. The concept can be utilized to develop high therapeutic index NCE (New Chemical Entities) for other macrophage mediated diseases like tuberculosis and cancer.

Fractured tracheostomy tube presenting as a foreign body in a paediatric patient.

Tracheostomy tube fracture and aspiration into the tracheobronchial tree leading to airway obstruction is a dangerous complication after tracheostomy. We report a case of a fractured tracheostomy tube in a 6-year-old child who had been maintained on a tracheostomy tube for the past 5 years. The tracheostomy tube got fractured at the junction of the tube and neck plate, and impacted in the trachea and right main bronchus. Rigid bronchoscopy performed through the tracheostomy stoma to retrieve the fractured tracheostomy tube and the anaesthetic management during the period are discussed.

Diagnostic accuracy of bedside tests for predicting difficult intubation in Indian population: An observational study.

BACKGROUND: Unanticipated difficult intubation can be challenging to anesthesiologists, and various bedside tests have been tried to predict difficult intubation. AIMS: The aim of this study was to determine the incidence of difficult intubation in the Indian population and also to determine the diagnostic accuracy of bedside tests in predicting difficult intubation. SETTINGS AND DESIGN: In this study, 200 patients belonging to age group 18-60 years of American Society of Anesthesiologists I and II, scheduled for surgery under general anesthesia requiring endotracheal intubation were enrolled. Patients with upper airway pathology, neck mass, and cervical spine injury were excluded from the study. MATERIALS AND METHODS: An attending anesthesiologist conducted preoperative assessment and recorded parameters such as body mass index, modified Mallampati grading, inter-incisor distance, neck circumference, and thyromental distance (NC/TMD). After standard anesthetic induction, laryngoscopy was performed, and intubation difficulty assessed using intubation difficulty scale on the basis of seven variables. STATISTICAL ANALYSIS: The Chi-square test or student t-test was performed when appropriate. The binary multivariate logistic regression (forward-Wald) model was used to determine the independent risk factors. RESULTS: Among the 200 patients, 26 patients had difficult intubation with an incidence of 13%. Among different variables, the Mallampati score and NC/TMD were independently associated with difficult intubation. Receiver operating characteristic curve showed a cut-off point of 3 or 4 for Mallampati score and 5.62 for NC/TMD to predict difficult intubation. CONCLUSION: The diagnostic accuracy of NC/TM ratio and Mallampatti score were better compared to other bedside tests to predict difficult intubation in Indian population.

Postoperative analgesia after inguinal hernia repair - Comparison of ropivacaine with bupivacaine: A randomized controlled trial.

BACKGROUND: Postoperative pain management by surgical site infiltration has an edge over other methods of analgesia as it is simple and has lesser side effects. This study was designed to compare the analgesic effects provided by bupivacaine, a classical long-acting local anesthetic and ropivacaine, a new amino amide local anesthetic agent. SUBJECTS AND METHODS: Ninety patients scheduled for elective inguinal herniorrhaphy were randomly allocated to one of the three groups: Group I - R 0.5, group II - R 0.25, and group III - B 0.25. General anesthesia was given. The surgical site was infiltrated before incision with 20 ml of drugs - ropivacaine 0.5% in group I, ropivacaine 0.25% in group II, bupivacaine 0.25% in group III. Intraoperatively hemodynamics were recorded every 15 min until the end of surgery and at the time of skin incision, at the time of cord pulling, and at the time of skin closure. Postoperatively, rest pain, pain on coughing, and pain on movements were assessed using visual analog scale (VAS) score immediately at the end of the surgery and hourly up to 4 h. The time of the first request for rescue analgesia was noted. RESULTS: VAS scores at rest, during coughing and movements were higher in group R 0.25 and the time of rescue analgesia was shorter with group R 0.25 when compared with other groups. CONCLUSION: Ropivacaine is less potent than bupivacaine at equal concentrations.

Complications in the use of bilateral inferiorly based nasolabial flaps for advanced oral submucous fibrosis.

Surgical management of advanced oral submucous fibrosis (OSMF) using bilateral inferiorly based nasolabial flaps is becoming increasingly popular. However no comprehensive analysis of delayed complications using this technique is available in the literature. The authors have conducted a retrospective study to examine the delayed complications of bilateral inferiorly based nasolabial flaps used in advanced oral submucous fibrosis at their institute along with a detailed review of literature on the subject. Thirty-two patients from January 2004 to December 2015 with OSMF and an interincisal distance less than 15 mm were included. All patients were treated with bilateral inferiorly based nasolabial flaps for correction of the restricted mouth opening. All patients had postoperative physiotherapy and were followed up for a minimum period of 6 months. All complaints of patients during the follow up phase were included in this study. In this series, complications such as partial necrosis, intra-oral hair growth, unacceptable extra-oral scar, wound dehiscence, orocutaneous fistula, and pincushioning effect were observed. Numerous complications can occur with the use of nasolabial flaps for the management of advanced oral submucous fibrosis. Although most complications are of inconsequential nature the surgeon must observe due diligence when using this flap.

Cross reactive molecules of human lymphatic filaria Brugia malayi inhibit Leishmania donovani infection in hamsters.

Coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. Earlier we showed that immunization with BmAFII (Sephadex G-200 eluted) fraction of human lymphatic filaria Brugia malayi inhibited progression of Leishmania donovani infection in golden hamsters. In the present study we identified cross reactive molecules of B. malayi, and investigated their effect on L. donovani infection and associated immune responses in the host. The sequence alignment and sharing of linear T- and B-cell epitopes in protein molecules of B. malayi and L. donovani counterparts were studied in silico. Hamsters were immunized with robustly cross reactive SDS-PAGE resolved fractions F6 (54.2-67.8kDa) and F9 (41.3-45.0kDa) of B. malayi and subsequently inoculated with amastigotes of L. donovani intracardially. F6 inhibited (∼72%) L. donovani infection and upregulated Th1 cytokine expression, lymphoproliferation, IgG2, IgG2/3 levels and NO production, and downregulated Th2 cytokine expression. Sequences in HSP60 and EF-2 of F6 and L. donovani counterparts were conserved and B- and T-cell epitopes in the proteins shared antigenic regions. In conclusion, leishmania-cross reactive molecules of filarial parasite considerably inhibited leishmanial infection via Th1-mediated immune responses and NO production. Common B- and T-cell epitope regions in HSP60 and EF-2 of the parasites might have contributed to the inhibitory effect on the L. donovani infection. Thus, leishmania-cross reactive filarial parasite molecules may help in designing prophylactic(s) against L. donovani.

Leptin augments protective immune responses in murine macrophages and enhances potential of miltefosine against experimental visceral leishmaniasis.

Adverse side effects and drug resistance issues are the two most important drawbacks which influence the widespread use of existing antileishmanial drugs. Use of immune stimulating agent with standard antileishmanial might be helpful to minimize the toxic effect of drug, shorten the dose regimen and delay the emergence of resistance. In the present study, we explored the in vitro immunomodulatory potential of an immunomodulator, leptin with lower concentration of standard drug, miltefosine. The level of Th1/Th2 cytokines, production of nitric oxide and reactive oxygen species and phagocytic activity was assessed by ELISA, Griess reaction and flow cytometric analysis, respectively. Leptin at a concentration of 15µg/mL showed heightened level of Th1 cytokines and nitric oxide generation from murine macrophages (J-774A.1 cells). Leptin (15µg/mL) also reduces the effective concentration of miltefosine by 2-folds from 7.5µM to 3.7µM. When given in conjunction with lower concentration of miltefosine (4µM), leptin (15µg/mL) significantly (***p<0.001) elevated the level of IL-12 (7.7 fold), TNF-α (8.1 fold) and nitric oxide (6.6 fold) along with markedly (***p<0.001) suppressed level of IL-10 and TGF-ß when compared with untreated infected macrophages. Leptin plus miltefosine also induces the phagocytic ability (**p<0.01) of macrophages in comparison to leptin alone and miltefosine alone treated groups. These finding illustrate that leptin activates host macrophages to generate protective immune response for the successful elimination of Leishmania parasite at lower concentration of miltefosine and has potential for further exploration in experimental animal model of visceral leishmaniasis (VL).

Chemotherapy of leishmaniasis part XIII: design and synthesis of novel heteroretinoid-bisbenzylidine ketone hybrids as antileishmanial agents.

Some novel heteroretinoid-bisbenzylidine ketone hybrids have been synthesized and evaluated for their in vitro antileishmanial activity against intramacrophagic amastigotes of Leishmania donovani. Among all the nine synthetic compounds, five compounds (7c, 7d and 7f-h) have shown significant (less than 7µM) activity against intramacrophagic amastigotes. The IC50 values of these compounds were found better than the reference drugs sodium stibogluconate (SSG) and miltefosine. This study helped us in identifying the new class of compounds that could be exploited as potent antileishmanial agents.

Simultaneous removal of pesticides from water by rice husk ash: batch and column studies.

The present study evaluated rice husk ash (RHA) as an adsorbent for simultaneous removal of a mixture of seven different pesticides (alachlor, metolachlor, chlorpyriphos, fipronil, α-endosulfan, ß-endosulfan, and p,p'-DDT) and two metabolites (p,p'-DDE and endosulfan sulfate) from water. The adsorbent RHA was prepared in the laboratory and characterized by techniques such as X-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy/energy-dispersive X-ray spectrometry. Adsorption kinetics were well described by the pseudo-second-order kinetic model. The Freundlich isotherm model fitted the equilibrium data better than the Langmuir model, and the maximum sorption capacity varied from 0.078 to 0.166 mg/g. The column elution studies showed that 10 L of mixed pesticide-contaminated water (0.05 mg/L) can be treated with only 10 g of RHA at a removal efficiency of 90%. The results implied that RHA can be used as a low-cost, easily available, and efficient adsorbent for the simultaneous removal of pesticides from contaminated water.

Simultaneous removal of multiple pesticides from water: effect of organically modified clays as coagulant aid and adsorbent in coagulation-flocculation process.

Contamination of drinking water sources with agrochemical residues became a major concern in the twenty-first century. Coagulation-flocculation is the most widely used water-treatment process, but the efficiency to remove pesticides and other organic pollutants are limited compared to adsorption process. Thus, simultaneous action of adsorption on normal bentonite or organo-modified montmorillonite clays [modified with octadecylamine (ODA-M) and octadecylamine + amino-propyltriethoxysilane (ODAAPS-M)] followed by coagulation-flocculation by alum and poly aluminium chloride has been evaluated for removal of 10 different pesticides, namely atrazine, lindane, metribuzin, aldrin, chlorpyriphos, pendimethalin, alpha-endosulphan, beta-endosulphan, p,p'-DDT, cypermethrin and two of its metabolites, endosulphan sulphate and p,p'-DDE, from water. The coagulation without integration of adsorption was less effective (removal % varies from 12 to 49) than the adsorption-coagulation integrated system (removal % varies from 71 to 100). Further, coagulation integrated with adsorption was more effective when organically modified montmorillonite was used as adsorbent compared to normal bentonite. The removal efficiency of organic clay depends upon the concentration of pesticides, doses of clay minerals, and efficiency was more for ODAAPS-M as compared to ODA-M. The combination of ODAAPS-M-clay with coagulants was also used efficiently for the removal of pesticides from natural and fortified natural water collected and the results exhibit the usefulness of this remediation technique for application in water decontamination and in treatment of industrial and agricultural waste waters.

Synthesis and biological evaluation of chalcones as potential antileishmanial agents.

Antileishmanial activities of thirty-five synthetic chalcones have been examined. Among them, ten compounds (4, 6, 16, 22, 23, 24, 25, 29, 35 and 37) exhibited potent in vitro activity (IC50 range from 1.70 to 8 µM) against extracellular promastigotes and intracellular amastigotes form of Leishmania donovani. Two promising compounds 22 and 37 were tested in vivo in L. donovani/hamster model. Chalcone 37 showed 83.32% parasite inhibition at a dose of 50 mg/kg for 10 days whereas, 75.89% parasite inhibition at 100 mg/kg dose for 5 days by intraperitoneal route at day 7 post-treatment.

Synthesis, structure-activity relationships, and biological studies of chromenochalcones as potential antileishmanial agents.

Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, 16, 17, and 22, were tested in a L. donovani/hamster model. Oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound 16 has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound 16 has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis.

Design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents.

An analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. These molecules were tested for their in vitro and in vivo biological activity against Leishmania donovani. Metabolic stability of these compounds was also improved through the introduction of halogen substituents. Compound (26g), found to be the most active; exhibited an IC50 value of 0.2 µM and >180 fold selectivity. The hydrochloride salt of (26g) showed 84.26 ± 4.44 percent inhibition at 50 mg/kg × 5 days (twice daily, oral route) dose in L. donovani/hamster model. The efficacy was well correlated with the PK data observed which indicating that the compound is well distributed.