Solvent-free synthesis of heteroannulated carbazoles: a novel class of anti-tumor agents.

A series of novel carbazole analogues that hold pyrido, isoxazolo, pyrimido and pyrazolo templates were designed and synthesised in good yield by grinding conditions. All the synthesised compounds were screened for their anti-tumor activity and displayed enviable selective growth inhibition on HeLa cell line compared to AGS cell line. Among these compounds, compound 2-(3',4'-diethoxy-benzylidene)-6-methyl-2,3,4,9-tetrahydro-carbazol-1-one,6-chloro-2-(3',4'-diethoxy-benzylidene)-2,3,4,9-tetrahydro-carbazol-1one, 2-(3',4'-diethoxy-benzylidene)-8-methyl-2,3,4,9-tetrahydro-carbazol-1-one, 3-(3',4'-diethoxyphenyl)-7-methyl-4,5-dihydro-10H-isoxazolo[3,4-a]carbazole, 7-chloro-3-(3',4'-diethoxyphenyl)-4,5-dihydro-10H-isoxazolo[3,4-a]carbazole, 4-(3',4'-diethoxyphenyl)-2-ethoxy-8-methyl-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile, 8-chloro-4-(3',4'-diethoxyphenyl)-2-ethoxy-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile, 4-(3',4'-diethoxyphenyl)-2-ethoxy-10-methyl-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile were found to have promising anti-tumor properities with reference to the standard ellipticine against the HeLa cancer cell line. All these intermediates showed IC50 outranged the standard ellipticine. The same compounds showed moderate activity against AGS cancer cell lines. The efforts were undertaken to optimize potency and selectivity of this class of compounds.

10-Methyl-2-oxo-4-phenyl-2,11-di-hydro-pyrano[2,3-a]carbazole-3-carbo-nitrile.

In the title mol-ecule, C23H14N2O2, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1018 (8) Å]. The pyrrole ring makes dihedral angles of 4.44 (5), 3.84 (5), 2.18 (5) and 56.44 (5)° with the pyran, fused benzene rings and phenyl ring, respectively. In the crystal, pairs of N-H⋯O hydrogen bonds generate R 2 (2)(14) loops and a C-H⋯N inter-action is also found. Mol-ecules are further linked by a number of π-π interactions [centroid-centroid distances vary from 3.5702 (5) to 3.7068 (6) Å], forming a three-dimensional network.

(E)-2-[(Furan-2-yl)methyl-idene]-7-methyl-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title mol-ecule, C(18)H(15)NO(2), the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1317 (12) Å]. The pyrrole ring makes dihedral angles of 1.01 (8) and 18.56 (10)° with the benzene and furan rings, respectively. The cyclo-hexene ring adopts a half-chair conformation. In the crystal, pairs of N-H⋯O hydrogen bonds form an R(2) (2)(10) ring. Mol-ecules are further linked by C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.

7-Methyl-1-phenyl-1,10-di-hydro-pyrazolo-[3,4-a]carbazole.

In the title mol-ecule, C20H15N3, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1082 (15) Å]. The pyrrole ring makes dihedral angles of 3.17 (8)/4.10 (9), 7.20 (9) and 44.62 (9)° with the fused benzene, pyrazole and phenyl rings, respectively. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming an infinite chain along [010]. Mol-ecules are further linked by nine π-π [centroid-centroid distances vary from 3.6864 (11) to 3.9802 (11) Å] and one C-H⋯π inter-action, forming a three-dimensional network.

A Comparative Study on Predictive Validity of Modified Shock Index, Shock Index, and Age Shock Index in Predicting the Need for Mechanical Ventilation among Sepsis Patients in a Tertiary Care Hospital.

Introduction: The shock index (SI), modified shock index (MSI), and age multiplied by SI (ASI) are used to assess the severity of shock. They are also used to predict the mortality of trauma patients, but their validity for sepsis patients is controversial. The aim of this study is to assess the predictive value of the SI, MSI, and ASI in predicting the need for mechanical ventilation after 24 h of admission among sepsis patients. Methods: A prospective observational study was conducted in a tertiary care teaching hospital. Patients with sepsis (235) diagnosed based on systemic inflammatory response syndrome criteria and quick sequential organ failure assessment were included in the study. The need for mechanical ventilation after 24 h is the outcome variables MSI, SI, and ASI were considered as predictor variables. The utility of MSI, SI, and ASI in predicting mechanical ventilation was assessed by receiver operative curve analysis. Data were analyzed using coGuide. Results: Among the study population, the mean age was 56.12 ± 17.28 years. MSI value at the time of disposition from the emergency room had good predictive validity in predicting mechanical ventilation after 24 h, as indicated by the area under the curve (AUC) of 0.81 (P < 0.001), SI and ASI had fair predictive validity for mechanical ventilation as indicated by AUC (0.78, P < 0.001) and (0.802, P < 0.001), respectively. Conclusion: SI had better sensitivity (78.57%) and specificity (77.07%) compared to ASI and MSI in predicting the need for mechanical ventilation after 24 h in sepsis patients admitted to intensive care units.

A ten year analysis of multi-drug resistant blood stream infections caused by Escherichia coli & Klebsiella pneumoniae in a tertiary care hospital.

BACKGROUND & OBJECTIVES: Extensive use of antibiotics has added to the escalation of antibiotic resistance. This study was undertaken to evaluate the association, if any between antibiotic use and resistance in a hospital setting, and also detect the predominant mechanism of antibiotic resistance in Escherichia coli and Klebsiella pneumoniae over a period of 10 years. METHODS: In a retrospective study of 10 years, a total of 77,618 blood culture samples from 2000 to 2009 from indoor patients were screened and those yielding E. coli and K. pneumoniae were included in the study. Antibiotic susceptibility records as well as the percentage of ESBL producers were noted. A total of 423 isolates of 2009 were also screened for AmpC and carbapenemase production. Antibiotic consumption data of 10 years were analysed. RESULTS: ESBL producing E. coli increased from 40 per cent in 2002 to 61 per cent in 2009, similarly there was a significant (P<0.05) rise in resistance to cefotaxime (75 to 97%), piperacillin-tazobactum (55- 84%) and carbapenem (2.4-52%) in K. pneumoniae. A significant (P<0.05) association was observed between resistance and consumption of carbapenem and piperacillin and tazobactum consumption in K. pneumonia. INTERPRETATION & CONCLUSIONS: Our study demonstrated a rise in consumption and resistance to broad spectrum antimicrobial agents and also established an association between consumption and resistance to these antibiotics. Over a period of 10 years, the emergence of pan-resistance in K. pneumoniae could be due to the production of carbapenemases whereas ESBL production was the common mechanism of resistance in E. coli. This study warrants a directed effort towards continued surveillance and antibiotic stewardship to minimize selection pressure and spread.

2-Chloro-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title mol-ecule, C(13)H(12)ClNO, the dihedral angle between the benzene and pyrrole rings is 1.38 (9)°. The cyclo-heptene ring adopts a distorted twist chair and sofa conformation. Inter-molecular N-H⋯O hydrogen bonds form an R(2) (2)(10) loop in the crystal packing. Further, weak C-H⋯O and C-H⋯π (involving the benzene ring) inter-actions are found in the crystal structure.

The impact of alcohol intoxication on early Glasgow Coma Scale-Pupil reactivity score in patients with traumatic brain injury: A prospective observational study.

Background: A simple arithmetic combination of the Glasgow Coma Scale (GCS) score and pupillary response, the GCS-Pupil (GCS-P), extends the information provided about the patient outcome to an extent comparable to that obtained using more complex methods. The objective of the study was to compare the changes in the GCS-P score of patients with traumatic brain injury (TBI) under alcohol intoxication and nontoxication over time. Methods: A prospective observational study was done in a hospital at the Level I trauma center. The patients admitted to the emergency department (ED) with TBI were the study participants. They were grouped into intoxicated and nonintoxicated based on blood alcohol concentration (BAC). BAC of 0.08% and above was considered intoxication. GCS-P score in the ED and the best day 1 GCS-P score were the outcome variables. For nonnormally distributed quantitative parameters, medians and interquartile range were compared between study groups using Mann-Whitney U-test. P <0.05 was considered statistically significant. Results: A total of 216 patients were included in the final analysis. There was no statistically significant difference between BAC in GCS-P score at different follow-up periods, GCS-P score (ED), and GCS-P score (best day 1). Conclusion: This prospective observational study showed a low GCS-P score for alcohol-intoxicated patients compared to nonintoxicated patients, which was not statistically significant. There was no significant difference in emergency GCS-P score and best day 1 score between alcohol-intoxicated and nonintoxicated patients.

7-(4-Meth-oxy-phen-yl)-4,9-dimethyl-N-(4-methyl-phen-yl)-5,12-diaza-tetra-phen-6-amine.

In the title compound, C(32)H(27)N(3)O, the fused tetra-cycilc ring system is essentially planar [r.m.s. deviation = 0.07 (7) Å]. An intra-molecular N-H⋯π(arene) inter-action and a weak intra-molecular C-H⋯N hydrogen bond may influence the mol-ecular conformation. In the crystal, weak inter-molecular C-H⋯N hydrogen bonds link the mol-ecules into centrosymmetric dimers, forming R(2) (2)(14) motifs. In addition, weak π-π stacking inter-actions with centroid-centroid distances in the range 3.578 (1)-3.739 (1) Šprovide further stabilization.

6-Methyl-2,3,4,9-tetra-hydro-1H-carbazole-1-thione.

In the title mol-ecule, C(13)H(13)NS, the dihedral angle between the benzene ring and the fused pyrrole ring is 0.71 (8)° and the cyclo-hexene ring is in an envelope form. The (CH(2))(3) atoms of the cyclo-hexene ring are disordered over two positions; the site-occupancy factor for the major component refined to 0.862 (4). In the crystal, inter-molecular N-H⋯S hydrogen bonds lead to the formation of centrosymmetric aggregates via an R(2) (2)(10) ring.

9-Ethyl-N-(3-nitro-benzyl-idene)-9H-carbazol-3-amine.

The title compound, C(21)H(17)N(3)O(2), crystallizes with two mol-ecules in the asymmetric unit. The carbazole groups show relatively small deviations from planarity [maximum displacements from the mean carbazole plane are 0.077 (7) and 0.101 (7) Å]. The dihedral angles between the 3-nitro-benzyl-idene-amine and carbazole groups are 37.9 (1) and 37.0 (1)° in the two mol-ecules.

4-Chloro-6-methyl-N-(4-methyl-phen-yl)quinolin-2-amine.

In the title compound C(17)H(15)ClN(2), the dihedral angle between the quinoline ring system and the phenyl ring is 50.18 (6)°. In the crystal, mol-ecules are linked into chains running along the c axis by N-H⋯N hydrogen bonds.

5-Methyl-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title mol-ecule, C(14)H(15)NO, the dihedral angle between the benzene and pyrrole rings is 1.99 (12)°. The cyclo-heptene ring adopts a slightly distorted boat conformation.

Synthesis and crystal structure of 1-hy-droxy-8-methyl-9H-carbazole-2-carbaldehyde.

Two crystallographically independent mol-ecules are present in the asymmetric unit of the title compound, C14H11NO2, with virtually identical geometries. The carbazole units are planar. The hy-droxy group at position 1, carbaldehyde group at position 2, and methyl group at position 8 (with the exception of two H atoms) are coplanar with the attached benzene rings. The dihedral angle between the two benzene rings is 2.20 (9)° in mol-ecule A and 2.01 (9)° in mol-ecule B. The pyrrole ring makes dihedral angles of 0.82 (10) and 1.40 (10)° [0.84 (10) and 1.18 (10)° in mol-ecule B] with the (-CH3)-substituted and (-OH and -CHO) substituted benzene rings, respectively. The mol-ecular structure is stabilized by the intra-molecular O-H⋯O hydrogen bonds, while the crystal structure features N-H⋯O and C-H⋯O hydrogen bonds. A range of π-π contacts further stabilizes the crystal structure.

Modified Shock Index as an Indicator for Prognosis Among Sepsis Patients With and Without Comorbidities Presenting to the Emergency Department.

OBJECTIVES: Modified shock index (MSI) is a simple bedside tool used in the emergency department. There are a few studies suggesting MSI as a good prognostic indicator than shock index in sepsis patients. However, there is not enough research emphasizing the role of MSI in patients with comorbidities. Hence, this study aims to assess the predictive validity of MSI in predicting the prognosis of sepsis patients with and without co-morbidities. METHODS: From January to December 2020, a prospective observational study was conducted in a tertiary care teaching hospital. Patients with sepsis diagnosed based on systemic inflammatory response syndrome criteria and quick sequential organ failure assessment (qSOFA) were included. The need for mechanical ventilation and step down from the intensive care unit were outcome variables, MSI was considered as a predictor variable, and co-morbidities as an explanatory variable. RESULTS: Among people with co-morbidities, the MSI value on arrival to the emergency department had fair predictive validity in predicting the need for mechanical ventilation after 24 hours, as indicated by the area under the curve of 0.749 (95% CI: 0.600-0.897; p-value = 0.002) and a sensitivity of 68.75% in predicting mechanical ventilation after 24 hours (MSI ≥ 1.59). Among people without co-morbidities, the MSI value on arrival to the emergency department had fair predictive validity in predicting the need for mechanical ventilation after 24 hours, as indicated by the area under the curve of 0.879 (95% CI: 0.770-0.988; p-value <0.001) and a sensitivity of 83.33% in predicting the need for mechanical ventilation after 24 hours (MSI ≥ 1.67). CONCLUSION: MSI can be used as an indicator in predicting the prognosis of sepsis patients in the emergency department. A simple bedside calculation of the MSI can indicate the need for mechanical ventilation and step down from the intensive care unit after 24 hours in patients with co-morbidities and without co-morbidities.

Surveillance of multidrug resistant organisms in tertiary care hospital in Delhi, India.

Surveillance of multi drug resistant organisms in a health care setting is a necessity to have optimum treatment out come and less of treatment failures. Once any health care setting gets colonized with multi drug resistant organisms, it is very difficult to decontaminate the environment. On review of our data, for 12 months of year 2008 the prevalence of difficult to treat organisms with poor clinical outcome especially in ICUs have been identified. The need for surveillance, prescription auditing & computer assisted retrieval of data has been emphasized and discussed in detail with respect to various high quality samples like blood, urine, respiratory, pus and sterile body fluids. The prevalence of MRSA & VRE has been documented 30 to 40% and 10%, respectively. Over all prevalence of penicillin intermediate resistant Streptococcus pneumoniae was found to be 9.52%. ESBL, AmpC, and Carbapenemase producing organisms were found to be 40 to 60%, 70 to 80% & 2 to 80% respectively in various multi drug resistant organisms like E. coli, Klebsiella spp., Pseudomonas spp. and Acinetobacter spp. 8% Pseudomonas spp. were found to be resistant to colistin in ICU samples. Enteric organisms were found to have high level ciprofloxacin resistant in 21.6% isolates, while S. paratyphi A isolation increased over a period of time. Yeast fungi isolated from blood predominantly were non-candida albicans (84.8%).

2-(2,3,4,9-Tetra-hydro-1H-carbazol-1-ylidene)propane-dinitrile.

In the title mol-ecule, C(15)H(11)N(3), the dihedral angle between the benzene ring and the fused pyrrole ring is 1.07 (5)°. The cyclo-hexene ring adopts an envelope conformation: the dicyano-methyl-ene group at position 1 has a coplanar orientation. An intra-molecular N-H⋯N hydrogen bond generates an S(7) ring motif. Inter-molecular N-H⋯N hydrogen bonds form an R(2) (2)(14) ring in the crystal. A C-H⋯π inter-action involving the benzene ring is also found in the structure.

2-Chloro-7-methyl-12-phenyldibenzo[b,g][1,8]naphthyridin-11(6H)-one.

In the title compound, C(23)H(15)ClN(2)O, the fused ring system is planar: the deviation of all the non-H atoms from the plane through all four fused rings is less than 0.31 Å. The plane of the phenyl ring is inclined at 71.78 (5)° to the mean plane of the 1,8-naphthrydine ring system. The crystal structure is devoid of any classical hydrogen bonds but π-π inter-actions are present.

4-Chloro-2,5-dimethyl-quinoline.

Mol-ecules of the title compound, C(11)H(10)ClN, are essentially planar (r.m.s. deviation for all non-H atoms = 0.009 Å) and are stacked along the a axis with the centroids of the benzene and pyridine rings alternately separated by 3.649 (1) and 3.778 (1) Å.

8-Methyl-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title compound, C(13)H(13)NO, the dihedral angle between the benzene ring and the fused pyrrole ring is 0.96 (7)°. The cyclohexenone ring adopts an envelope conformation. Inter-molecular N-H⋯O hydrogen bonds form R(2) (2)(10) ring motifs in the crystal structure. Weak C-H⋯π inter-actions involving the benzene ring also occur.