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1.
BMC Gastroenterol ; 24(1): 119, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528470

RESUMO

INTRODUCTION: Acute pancreatitis poses a significant health risk due to the potential for pancreatic necrosis and multi-organ failure. Fluid resuscitation has demonstrated positive effects; however, consensus on the ideal intravenous fluid type and infusion rate for optimal patient outcomes remains elusive. METHODS: A comprehensive literature search was conducted using PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between 2005 and January 2023. Reference lists of potential studies were manually searched to identify additional relevant articles. Randomized controlled trials and retrospective studies comparing high (≥ 20 ml/kg/h), moderate (≥ 10 to < 20 ml/kg/h), and low (5 to < 10 ml/kg/h) fluid therapy in acute pancreatitis were considered. RESULTS: Twelve studies met our inclusion criteria. Results indicated improved clinical outcomes with low versus moderate fluid therapy (OR = 0.73; 95% CI [0.13, 4.03]; p = 0.71) but higher mortality rates with low compared to moderate (OR = 0.80; 95% CI [0.37, 1.70]; p = 0.55), moderate compared to high (OR = 0.58; 95% CI [0.41, 0.81], p = 0.001), and low compared to high fluids (OR = 0.42; 95% CI [0.16, 1.10]; P = 0.08). Systematic complications improved with moderate versus low fluid therapy (OR = 1.22; 95% CI [0.84, 1.78]; p = 0.29), but no difference was found between moderate and high fluid therapy (OR = 0.59; 95% CI [0.41, 0.86]; p = 0.006). DISCUSSION: This meta-analysis revealed differences in the clinical outcomes of patients with AP receiving low, moderate, and high fluid resuscitation. Low fluid infusion demonstrated better clinical outcomes but higher mortality, systemic complications, and SIRS persistence than moderate or high fluid therapy. Early fluid administration yielded better results than rapid fluid resuscitation.


Assuntos
Pancreatite Necrosante Aguda , Ressuscitação , Humanos , Doença Aguda , Estudos Retrospectivos , Ressuscitação/métodos , Hidratação/métodos
2.
Arch Pharm (Weinheim) ; 356(3): e2200361, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36494101

RESUMO

Continued emerging resistance of pathogens against the clinically approved candidates and their associated limitations continuously demand newer agents having better potency with a more suited safety profile. Quinoline nuclei containing scaffolds of natural and synthetic origin have been documented for diverse types of pharmacological activities, and a number of drugs are clinically approved. In the present review, we unprecedentedly covered the biological potential of 4-substituted quinoline and elaborated a rationale for its special privilege to afford the significant number of approved clinical drugs, particularly against infectious pathogens. Compounds with 4-substituted quinoline are well documented for antimalarial activity, but in the last two decades, they have been extensively explored for activity against cancer, tuberculosis, and several other pathogens including viruses, bacteria, fungi, and other infectious pathogens. In the present study, the anti-infective spectrum of this scaffold is discussed against viruses, mycobacteria, malarial parasites, and fungal and bacterial strains, along with recent updates in this area, with special emphasis on the structure-activity relationship.


Assuntos
Anti-Infecciosos , Antimaláricos , Quinolinas , Cloroquina/farmacologia , Relação Estrutura-Atividade , Anti-Infecciosos/farmacologia , Quinolinas/farmacologia , Antimaláricos/farmacologia , Bactérias
3.
Cureus ; 14(7): e27119, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36000095

RESUMO

A pancreatic mass is mostly discovered late in the course of the disease and is usually asymptomatic in the early stages. In rare cases, a pancreatic mass may be metastatic, and presentation may depend on the presence and locations of other metastasis or to the primary lesion. Renal cell cancer is the most common tumor presenting as metastatic pancreatic mass. Most metastases occur within the first ten years after diagnosis. We present a case of metastatic renal cell cancer to the contralateral adrenal and pancreas causing pancreatic duct dilation, 15 years after radical nephrectomy.

4.
Cureus ; 14(12): e32167, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36605060

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic inflammatory disease. Multiple risk factors have been defined for the manifestation of HLH. While infection remains the top risk factor, having multiple surgical procedures has also been suggested as a potential risk factor for HLH. Our patient presented with generalized weakness, weight loss, and fatigue after having a greenlight laser prostatectomy for benign prostate hypertrophy; the patient deteriorated rapidly and was found to fulfill the HLH 2004 and modified criteria. We believe this patient had a rare bone marrow disorder with a rare complicated clinical and laboratory presentation.

5.
Expert Opin Drug Discov ; 16(10): 1119-1147, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33908322

RESUMO

Introduction: Cancer is a dreadful disorder that is emerging as one of the leading causes of mortality across the globe. The complex tumor environment, supplemented with drawbacks of the existing drugs, has made it a global health concern. The Tetrahydroisoquinoline (THIQ) ring holds an important position in medicinal chemistry due to its wide range of pharmacological properties. Several THIQ based natural products have been previously explored for their antitumor properties, making it a vital scaffold for anticancer drug design.Areas covered: This review article addresses the potential of THIQ as anticancer agents. Various medicinal chemistry strategies employed for the design and development of THIQ analogs as inhibitors or modulators of relevant anticancer targets have been discussed in detail. Moreover, the common strategies employed for the synthesis of the core scaffold are also highlighted.Expert opinion: Evidently, THIQs have tremendous potential in anticancer drug design. Some of these analogs exhibited potent activity against various cancer molecular targets. However, there are some drawbacks, such as selectivity that need addressing. The synthetic ease for constructing the core scaffold complimented with its reactivity makes it ideal for further structure-activity relationship studies. For these reasons, THIQ is a privileged scaffold for the design and development of novel anticancer agents.


Assuntos
Antineoplásicos , Neoplasias , Tetra-Hidroisoquinolinas , Antineoplásicos/química , Desenho de Fármacos , Humanos , Neoplasias/tratamento farmacológico , Relação Estrutura-Atividade , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/farmacologia , Tetra-Hidroisoquinolinas/uso terapêutico
6.
Indian J Surg Oncol ; 11(3): 401-405, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33013118

RESUMO

Treatment of maxillary sinus cancer poses several challenges because of its complex anatomy, close proximity to critical structures and majority of patients presenting at an advanced stage. Despite presence of several treatment approaches, the outcome in these cancers has remained dismal. This article examines its clinical behaviour and treatment outcome of these patients treated at our centre in past 7 years. In this retrospective study, 67 patients with carcinoma of maxillary sinus presented from January 2011 to December 2017 were analysed. All the patients reporting during this period were included except those who did not turn up after first visit. Of all the patients, 64.2% had squamous cell carcinoma. The majority of patients presented with advanced stage (IVA and IVB, 83.58%). Nodal disease at presentation was seen in seven patients (10.4%). Treatment to the primary site comprised of surgery and radiotherapy in 24 patients, radiotherapy alone in 22 patients and surgery alone in 12 patients. Statistical program for social sciences (SPSS) version 16 was used for all statistical analyses. The mean follow-up time was 25 months (range 3-72 months). Overall, 17 out of 41 patients who were treated with curative intent (41.5%) developed recurrence. Patients who underwent surgery followed by adjuvant radiotherapy did fairly better in terms of recurrence. Seven patients out of 17 (41.2%) could be salvaged by surgery or radiation. Only one patient developed distant metastasis to D8 vertebra. Patients who were treated with surgery and radiotherapy (either preoperative/adjuvant setting) had better disease-free survival. The results of the current study regarding the treatment of carcinoma of the maxillary sinus show feasibility and efficacy of multimodal therapy. Radical radiotherapy appears to be a feasible alternative in cases of inoperable tumours. Loco regional relapse remains a significant pattern of failure.

7.
Indian J Otolaryngol Head Neck Surg ; 71(Suppl 1): 62-65, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31741932

RESUMO

Epithelial myoepithelial carcinoma (EMC) is a rare biphasic tumor of salivary glands with low malignant potential. Although known to occur in submandibular gland and minor salivary glands, its most common location is parotid. Clinical and radiological findings often mimic a benign tumor. Because of rarity of EMC a standard treatment guideline is not yet known. Surgical resection is the most widely used approach. Although it is a low grade tumor, local recurrence rates of 23-50 % have been reported with 25 % chance of distant metastasis. Patients with histo-pathologic markers of aggressive disease should be considered for adjuvant radiotherapy. We report a case of epithelial myoepithelial carcinoma of parotid in a 40 year male that was treated with surgery followed by post-operative radiotherapy.

8.
Front Plant Sci ; 9: 937, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013590

RESUMO

Micronutrient deficiency, also known as "hidden hunger," is an increasingly serious global challenge to humankind. Among the mineral elements, Fe (Iron) and Zn (Zinc) have earned recognition as micronutrients of outstanding and diverse biological relevance, as well as of clinical importance to global public health. The inherently low Fe and Zn content and poor bioavailability in cereal grains seems to be at the root of these mineral nutrient deficiencies, especially in the developing world where cereal-based diets are the most important sources of calories. The emerging physiological and molecular understanding of the uptake of Fe and Zn and their translocation in cereal grains regrettably also indicates accumulation of other toxic metals, with chemically similar properties, together with these mineral elements. This review article emphasizes breeding to develop bioavailable Fe- and Zn-efficient cereal cultivars to overcome malnutrition while minimizing the risks of toxic metals. We attempt to critically examine the genetic diversity regarding these nutritionally important traits as well as the progress in terms of quantitative genetics. We sought to integrate findings from the rhizosphere with Fe and Zn accumulation in grain, and to discuss the promoters as well as the anti-nutritional factors affecting Fe and Zn bioavailability in humans while restricting the content of toxic metals.

9.
J Neurooncol ; 139(1): 153-166, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29633112

RESUMO

BACKGROUND: The treatment of primary CNS lymphoma (PCNSL) comprises high dose methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy (WBRT), the major drawback of which is long term neurotoxicity. We intended to assess the feasibility of response adapted WBRT in PCNSL in the Indian setting. METHODS: We screened 32 patients and enrolled 22 eligible patients with PCNSL from 2015 to 2017 in a prospective phase II trial. The patients underwent five 2-weekly cycles of induction chemotherapy with rituximab, methotrexate, vincristine, procarbazine. Patients with complete response(CR) to induction chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks while those with partial response (PR), stable or progressive disease (SD or PD) were given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter two cycles of consolidation chemotherapy with cytarabine were given. The primary endpoints of the study were assessment of response rate (RR) and progression free survival (PFS). The secondary endpoints of the study were assessment of overall survival (OS), toxicity profile of treatment and serial changes in quality of life and neuropsychological parameters. RESULTS: Out of 19 patients who completed HDMTX based chemotherapy, 10 (52.63%) patients achieved CR, 8 (42.11%) patients had PR and 1 patient had PD. After a median follow-up period of 11.25 months, the estimated median OS was 19 months. The actuarial rates of PFS and OS were respectively 94.1 and 68.2% at 1 year and 50.2 and 48.5% at 2 years. Three patients in reduced dose WBRT arm had recurrence and two of them died of progressive disease, whereas there was no recurrence or disease related death in standard dose WBRT arm. On univariate analysis of PFS, age ≤ 50 years and use of standard dose WBRT (45 Gy) led to significantly improved outcome (p value 0.03 and 0.02 respectively). CONCLUSION: In patients with PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due to higher risk of recurrence, progression and early death. Trial Registration No CTRI/2015/10/006268.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/terapia , Irradiação Craniana , Linfoma/terapia , Metotrexato/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/psicologia , Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Fracionamento da Dose de Radiação , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Linfoma/mortalidade , Linfoma/psicologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do Tratamento
10.
Eur J Med Chem ; 150: 559-566, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29549840

RESUMO

Molecular hybridization is a ligand based drug design approach is well known recent medicinal chemistry to design anti-parasitic agents. In the present study, we have designed a series of (1-phenyl-9H-pyrido [3,4-b]indol-3-yl) (4-phenylpiperazin-1-yl)methanone derivatives using molecular hybridization approach. Designed analogues were evaluated for cytotoxicity and inhibition activity against Leishmania infantum and Leishmania donovani. Among these reported analogues 7b, 7d, 7e, 7f and 7m displayed potent inhibition of both L. infantum and L. donovani. Compounds 7i and 7k exhibited selective potent inhibition of L. donovani. Especially, compounds 7e and 7k showed most potent anti-leishmanial activity against L. infantum and L. donovani respectively. Anti-leishmanial activity of these compounds is comparable with standard drugs miltefosine and pentamidine. SAR studies revealed that, electron donating group substitution on phenyl ring recommended for potent anti-leishmanial activity.


Assuntos
Antineoplásicos/farmacologia , Antiprotozoários/farmacologia , Carbolinas/farmacologia , Desenho de Fármacos , Leishmania donovani/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Piperazinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antiprotozoários/síntese química , Antiprotozoários/química , Carbolinas/síntese química , Carbolinas/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Leishmania donovani/citologia , Leishmania infantum/citologia , Estrutura Molecular , Testes de Sensibilidade Parasitária , Piperazinas/síntese química , Piperazinas/química , Relação Estrutura-Atividade
11.
Bioorg Chem ; 74: 158-165, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28802166

RESUMO

Quercetin is one of the naturally occurring polyphenol flavonoid predominantly known for antidiabetic activity. In the present study, by considering the structural requirements, twenty two novel chromone derivatives (5-26) as α-amylase inhibitor were designed and subsequently in silico evaluated for drug likeness behavior. Designed compounds were synthesized, characterized by spectral analysis and finally evaluated for the inhibition of α-amylase activity by in vitro assay. Tested compounds exhibited significant to weak activity with IC50 range of 12-125µM. Among the tested compounds, analogues 5, 8, 12, 13, 15, 17 and 22 exhibited significant human α-amylase inhibitory activity with IC50 values <25µM, which can be further explored as anti-hyperglycemic agents. Putative binding mode of the significant and least active α-amylase inhibitors with the target enzyme was also explored by the docking studies.


Assuntos
Cromonas/farmacologia , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , alfa-Amilases/antagonistas & inibidores , Cromonas/síntese química , Cromonas/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , alfa-Amilases/metabolismo
12.
Comb Chem High Throughput Screen ; 20(8): 734-746, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28641512

RESUMO

BACKGROUND: HIV integrase (IN) and reverse transcriptase (RT) are key enzymes for the replication of HIV-1. DNA polymerase and ribonuclease H (RNase H) are the two catalytic domains of HIV-1 RT which are validated as drug targets because of their essence for replication. IN and RNase H domain of RT shares striking structural similarity; it contains conserved DDE triad (two aspartates and one glutamate) and a pair of divalent Mg2+/Mn2+ ions at their catalytic core domain. OBJECTIVE: To search for novel compounds with dual inhibition of IN and RNase H for the drug development against both wild and drug-resistant strains of HIV. METHODS: In the present work, attempts have been made to search compounds against both IN and the RNase H domain of RT. Using structure-based virtual screening approach; Asinex database of small molecules was screened against the viral IN. Top thirty ranked hits obtained, were further evaluated against RNase H domain of RT using Extra Precision (XP) mode of Glide docking. Furthermore, eleven common potential hits were observed which were subjected to the in-silico prediction of drug-likeness properties. Later on, molecular dynamics simulation was performed for the best common active hit (AS6), in the complex with selected enzymes. RESULT: In silico screening of Asinex database compounds against IN and RNase H resulted in total seven compounds namely AS3, AS5, AS6, AS15, AS17, AS18, and AS20 having dual inhibition activity. CONCLUSION: This study warrants the dual inhibition activity of AS6 against IN and RNase H confirms its anti-HIV activity.


Assuntos
Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/metabolismo , Transcriptase Reversa do HIV/antagonistas & inibidores , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores da Transcriptase Reversa/farmacologia , Relação Dose-Resposta a Droga , HIV/enzimologia , Inibidores de Integrase de HIV/química , Transcriptase Reversa do HIV/metabolismo , Ligantes , Estrutura Molecular , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade
13.
J Pediatr Hematol Oncol ; 39(2): e62-e68, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28060113

RESUMO

The study was aimed at evaluating adherence to treatment protocol and outcome in pediatric parameningeal rhabdomyosarcoma (PM-RMS). We analyzed the characteristics, treatment administered, outcomes and patterns of failure of pediatric PM-RMS, who were treated with multimodality therapy between January 2005 and December 2013.Univariate and multivariate analysis (MVA) was completed to evaluate the impact of various prognostic factors. Thirty-seven patients were treated at our institution. Majority of them had the primary disease in paranasal sinuses (n=13). Majority of the patients belonged to group III (n=30) and stage III (n=24). The overall response rate to treatment was 52.5% (n=21). At a mean follow-up of 19.1 months, 23 patients developed disease progression. The actuarial rates of failure-free survival and overall survival (OS) at 2 years were 40% and 67.5%, respectively. Patients who received >20 weeks of intended chemotherapy schedule (P=0.02) and had complete response to first-line treatment (P=0.0004) were found to have superior failure-free survival on MVA. Complete response was the lone determinant of superior OS on MVA (P=0.006). Majority of patients with PM-RMS present with advanced stage disease. Response to first-line treatment is a significant predictor of superior progression-free survival and OS in these patients.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Cooperação do Paciente , Rabdomiossarcoma/epidemiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Institutos de Câncer/estatística & dados numéricos , Quimiorradioterapia , Criança , Pré-Escolar , Terapia Combinada , Irradiação Craniana , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Índia/epidemiologia , Lactente , Estimativa de Kaplan-Meier , Masculino , Cuidados Paliativos , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/cirurgia , Neoplasias dos Seios Paranasais/terapia , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Rabdomiossarcoma/patologia , Rabdomiossarcoma/cirurgia , Rabdomiossarcoma/terapia , Terapia de Salvação , Centros de Atenção Terciária/estatística & dados numéricos , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto Jovem
14.
Bioorg Chem ; 70: 100-106, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27939960

RESUMO

In the present study, we have reported synthesis and biological evaluation of a series of fifteen 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole derivatives against both promastigotes and amastigotes of Leishmania parasites responsible for visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis. Among these reported analogues, compounds 7b, 7c, 7f, 7g, 7i, 7j, 7m, 7o displayed potent activity (15.55, 7.70, 7.00, 3.80, 14.10, 9.25, 3.10, 4.85µM, respectively) against L. donovani promastigotes than standard drugs miltefosine (15.70µM) and pentamidine (32.70µM) with good selectivity index. In further, in-vitro evaluation against amastigote forms, two compounds 7g (8.80µM) and 7i (7.50µM) showed significant inhibition of L. donovani amastigotes. Standard drug amphotericin B is also used as control to compare inhibition potency of compounds against both promastigote (0.24µM) and amastigote (0.05µM) forms.


Assuntos
Antiprotozoários/química , Antiprotozoários/farmacologia , Indóis/química , Indóis/farmacologia , Leishmania/efeitos dos fármacos , Tiofenos/química , Tiofenos/farmacologia , Animais , Células Cultivadas , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Macrófagos/parasitologia , Camundongos
15.
J Clin Diagn Res ; 10(10): XC01-XC05, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27891440

RESUMO

INTRODUCTION: Orbital Granulocytic Sarcoma (OGS) is an uncommon manifestation associated with haematological malignancies. Chemotherapy remains the cornerstone of the treatment. The role of radiation is not well-defined. AIM: To evaluate the effect of radiation in OGS and to define an optimal dose for achieving adequate local control. MATERIALS AND METHODS: This was a retrospective analysis of 11 patients who received radiation therapy to orbit for Granulocytic Sarcoma (GS) between 2007 and 2014 at a tertiary cancer center in India. Radiotherapy was planned by three dimensional conformal (3DCRT) techniques. Demographic and disease characteristics, including clinical, imaging, histopathology and treatment details in this patient cohort were recorded and their response to therapy was assessed. RESULTS: The median age was 7 years (Range: 2-16 years). There were 3 female and 8 male patients. Eight patients were diagnosed as Acute Myelogenous Leukemia (AML), two patients had Primary Orbital Granulocytic Sarcoma (POGS) and one had bi-phenotypic leukemia. Median dose was 24.5Gy (Range-15-45 Gy). Two anterior oblique field design were used most commonly. Out of 11 patients, 5 (45.4%) had complete response, 3 (27.27%) had partial response, 1 patient had stable disease (9%) and 2 developed progressive disease (18%). Median follow-up was 24 months (Range 24-84 months). At last follow-up, 7 (63.6%) patients were alive and 4 patients (37.4%) were dead due to progressive disease. CONCLUSION: In patients with residual orbital disease after chemotherapy, low dose radiation can be used to improve local disease control and improve quality of life. Local conformal radiotherapy of 24-30 Gy in conventional fractionation appears optimal with excellent local control and minimal morbidity.

16.
Bioorg Chem ; 67: 75-83, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27288643

RESUMO

In the present study, fifteen novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propan-1-one (6a-o) derivatives were designed as inhibitor of HIV-1 RT using ligand based drug design approach and in-silico evaluated for drug-likeness properties. Designed compounds were synthesized, characterized and in-vitro evaluated for RT inhibitory activity against wild HIV-1 RT strain. Among the tested compounds, four compounds (6a, 6b, 6j and 6o) exhibited significant inhibition of HIV-1 RT (IC50⩽10µg/ml). All synthesized compounds were also evaluated for anti-HIV-1 activity as well as cytotoxicity on T lymphocytes, in which compounds 6b and 6l exhibited significant anti-HIV activity (EC50 values 4.72 and 5.45µg/ml respectively) with good safety index. Four compounds (6a, 6b, 6j and 6o) found significantly active against HIV-1 RT in the in-vitro assay were in-silico evaluated against two mutant RT strains as well as one wild strain. Further, titled compounds were evaluated for in-vitro antibacterial (Escherichia coli, Pseudomonas putida, Staphylococcus aureus and Bacillus cereus) and antifungal (Candida albicans and Aspergillus niger) activities.


Assuntos
Antibacterianos/farmacologia , Fármacos Anti-HIV/farmacologia , Antifúngicos/farmacologia , Desenho de Fármacos , Transcriptase Reversa do HIV/antagonistas & inibidores , Inibidores da Transcriptase Reversa/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Antifúngicos/síntese química , Antifúngicos/química , Bactérias/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fungos/efeitos dos fármacos , HIV/efeitos dos fármacos , Transcriptase Reversa do HIV/genética , Transcriptase Reversa do HIV/metabolismo , Testes de Sensibilidade Microbiana , Estrutura Molecular , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade
17.
Chem Biol Drug Des ; 88(4): 585-91, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27203404

RESUMO

In this study, seventeen novel quinoline-based carboxylic hydrazides were designed as potential anti-tubercular agents using molecular hybridization approach and evaluated in-silico for drug-likeness behavior. The compounds were synthesized, purified, and characterized using spectral techniques (like FTIR, (1) H NMR, and Mass). The in-vitro anti-tubercular activity (against Mycobacterium tuberculosisH37Ra) and cytotoxicity against human lung fibroblast cells were studied. Among the tested hydrazides, four compounds (6h, 6j, 6l, and 6m) exhibited significant anti-tubercular activity with MIC values below 20 µg/mL. The two most potent compounds of the series, 6j and 6m exhibited MIC values 7.70 and 7.13 µg/mL, respectively, against M. tuberculosis with selectivity index >26. Structure-activity relationship studies were performed for the tested compounds in order to explore the effect of substitution pattern on the anti-tubercular activity of the synthesized compounds.


Assuntos
Antituberculosos/síntese química , Antituberculosos/farmacologia , Desenho de Fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Quinolinas/síntese química , Quinolinas/farmacologia , Antituberculosos/química , Linhagem Celular Tumoral , Fibroblastos/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Quinolinas/química , Relação Estrutura-Atividade
18.
J Clin Diagn Res ; 9(10): XC05-XC07, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26557600

RESUMO

BACKGROUND & AIM: Adenoid cystic carcinoma (ACC) of lacrimal gland is a rare tumour with aggressive behaviour. There is sparse data to address optimum therapy for such tumours. So, the present study was aimed at evaluating the role of adjuvant three dimensional conformal radiotherapy (3D-CRT) in cases of incomplete (R1) resection along with review of literature pertaining to management of lacrimal adenoid cystic carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the demographic and treatment data of 10 biopsy proven ACC of lacrimal gland patients, treated from December 2006 to June 2013. They were treated with radiotherapy following surgical resection. Eight patients underwent gross total excision of the tumour mass (enbloc excision) followed by conformal radiotherapy to a dose of 60 Gray/30fractions/ 6 weeks. Two patients with advanced disease were treated with palliative radiotherapy after biopsy. RESULTS: The median age was 32 years. There were equal numbers of male and female patients. The median duration of symptoms was 7 months. At a median follow up of 21 months, eight patients had no evidence of disease and had complete tumour response, two patients worsened, and one of the two had systemic failure with bone metastasis. CONCLUSION: Despite a small sample size and short follow, enbloc surgical excision with adjuvant radiotherapy is well tolerated and shows good control in ACC of lacrimal gland.

19.
Asian Pac J Cancer Prev ; 16(16): 7025-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26514485

RESUMO

BACKGROUND: The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. MATERIALS AND METHODS: Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. RESULTS: The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. CONCLUSIONS: The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.


Assuntos
Carcinoma de Células Pequenas/terapia , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Neoplasias Orofaríngeas/terapia , Cuidados Paliativos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/secundário , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Neoplasias Esofágicas/patologia , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Orofaríngeas/patologia
20.
Asian Pac J Cancer Prev ; 16(12): 5075-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26163644

RESUMO

BACKGROUND: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco- regional control with a conventional schedule. MATERIALS AND METHODS: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin 40 mg/m2. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7 Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7 Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin 20 mg/m2/day was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. RESULTS: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were 65±12 and 48±4 days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade≥3 toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. CONCLUSIONS: In the setting of concurrent chemo- radiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.


Assuntos
Adenocarcinoma/terapia , Braquiterapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Cisplatino/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adenocarcinoma/patologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/patologia , Esquema de Medicação , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
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