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Fulltext Effects of cytochrome p450 inhibitors on itraconazole and fluconazole induced cytotoxicity in hepatocytes

Somchit N, Ngee CS, Yaakob A, Ahmad Z, Zakaria ZA

J Toxicol, 2009;2009:912320.
PMID: 20130764 DOI: 10.1155/2009/912320

Itraconazole and fluconazole have been reported to induce hepatotoxicity in patients. The present study was designed to investigate the role of cytochrome P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female rats were administered daily SKF 525A or curcumin (5 and 25 mg/kg). Control rats received an equivalent amount of dosed vehicle. The animals were anaesthetized 24 hours after receiving the last dose for liver perfusion. Hepatocytes were then exposed to various concentrations of antifungal drugs. In vitro incubation of hepatocytes with itraconazole revealed significantly lower viability when compared to fluconazole as assessed by lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase activities. The cytotoxicity of itraconazole was enhanced when incubated with hepatocytes pretreated with SKF 525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed to either increase or decrease the cytotoxicity of both antifungal drugs. ATP levels also showed significant decrease in both itraconazole and fluconazole incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly lower ATP levels after itraconazole incubations. Collectively, these results confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole induced hepatocyte toxicity. Differences of the effects of SKF 525A on the cytotoxicity induced by itraconazole and fluconazole may be due to the differences on the metabolism of each antifungal drug in vivo.

Matched MeSH terms: Fluconazole
Fulltext Should parental decision override best interest of a handicapped child? A case illustration in a Malaysian child with Down Syndrome

Fashiham Taib, Nur Arzuar Abdul Rahim, Mohd Rizal Mohd Zain, Mohamad Ikram Ilias, Nik Mohd Rizal Mohd Fakri, Zabidi Azhar Hussin

Education in Medicine Journal, 2015;7(1):67-71.
MyJurnal

The paper discusses on the complexity of the issues surrounding a patient with subluxation of cervical spine in a Down syndrome child. Several relevant issues are discussed including consent in a minor, conflicting decision making between parents and doctors, end-of-life issues, supporting handicapped child with minimal co-morbidities, community ethics, neglect of care by the caregiver and decision making after allowing zonal of parental discretion. Despite the difficulties surrounding parental actions, there are still ethical priorities which have to be considered individually to alleviate the suffering of the patients and the family members. Dealing with patients with chronic illnesses is a challenge for any medical doctors. The case warrants sensitive approach to allow appropriate respect for parental decision despite in disagreement with the clinical team. The term ‘zone of parental discretion’ refers to a controversial area of decision making; and has still many potential conflicts on day to day clinical cases, especially among the conservative society in the East Coast of Peninsular Malaysia.

Matched MeSH terms: Fluconazole
Fulltext Cryptococcal meningitis in an immunocompetent child: a case report and literature review

Othman N, Abdullah NA, Wahab ZA

Southeast Asian J. Trop. Med. Public Health, 2004 Dec;35(4):930-4.
PMID: 15916093

An immunocompetent 5 year-old girl presented with pyrexia of unknown origin associated with headache. Initial investigations showed leukocytosis and an increased erythrocyte sedimentation rate. A Widal-Weil Felix test, blood film for malarial parasites, mycoplasma IgM antibody, cultures from blood and urine, full blood picture, Mantoux test, and chest x-ray were all negative. A lumbar puncture was done as part of a work-up for pyrexia of unknown origin. Cryptococcus neoformans was seen on India ink examination and confirmed on culture. She was treated with 10 weeks of intravenous amphotericin B and 8 weeks of fluconazole. Further immunological tests did not reveal any defect in the cell-mediated immune system. C. neoformans meningitis may present with non-specific symptoms and should be considered in a work-up for pyrexia of unknown origin.

Matched MeSH terms: Fluconazole/therapeutic use
Fulltext A catheter-related bloodstream infection caused by the yeast Kodamaea ohmeri

Ding, C.H., Tzar M.N., Biswas S., Muttaqillah N.A.S., Wahab A.A.

International Medical Journal Malaysia, 2018;17(2):135-138.
MyJurnal

Catheter-related bloodstream infections caused by Kodamaea ohmeri are generally not considered due to the relative scarcity of reported cases. This is a case of an 85-year-old man with poorly controlled diabetes mellitus who was initially admitted to our hospital for diabetic ketoacidosis. An internal jugular catheter was inserted as part of the initial management. A week later the patient developed a temperature spike and a yeast identified as Kodamaea ohmeri by ID 32 C (bioMérieux, France) was isolated from both his central and peripheral blood cultures. The catheter was removed and the patient was treated with fluconazole despite the organism’s relatively high minimum inhibitory concentration (2 μg/mL) to this antifungal. The fungemia resolved following a 2-weeks course of fluconazole.

Matched MeSH terms: Fluconazole
Prevalence of albicans and non-albicans candiduria in a Malaysian medical centre

Ding CH, Wahab AA, Muttaqillah NA, Tzar MN

J Pak Med Assoc, 2014 Dec;64(12):1375-9.
PMID: 25842581

To determine the proportion of albicans and non-albicans candiduria in a hospital setting and to ascertain if fluconazole is still suitable as empirical antifungal therapy based on antifungal susceptibility patterns of Candida species.

Matched MeSH terms: Fluconazole/therapeutic use
Genetic diversity, antifungal susceptibility and enzymatic characterisation of Malaysian clinical isolates of Candida glabrata

Lotfalikhani A, Khosravi Y, Sabet NS, Na SL, Ng KP, Tay ST

Trop Biomed, 2018 Dec 01;35(4):1123-1130.
PMID: 33601859

Candida glabrata has been reported as the second or third most common yeast species isolated from patients with vaginitis and invasive candidiasis. This study was aimed to determine the genetic diversity, antifungal susceptibility and enzymatic profiles of C. glabrata isolated from vaginal and blood samples in the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre. A random amplified polymorphic DNA (RAPD) analysis method, using M13 and (GTG)5 primers, was used for strain differentiation of C. glabrata isolates. Antifungal susceptibility testing of C. glabrata isolates was determined using E-test against amphotericin B, caspofungin, fluconazole and voriconazole and microbroth dilution method against clotrimazole. The enzymic profiles of C. glabrata were determined using APIZYM semi-quantitation kit and egg-yolk agar method. A total of 14 RAPD patterns were identified amongst C. glabrata isolates investigated this study. Susceptibility to amphotericin B, caspofungin, fluconazole and voriconazole was noted. Approximately one third of the isolates demonstrated resistance to clotrimazole (MIC>=1 µg/ml). A single isolate of C. glabrata was resistant to caspofungin (MIC:1.5 µg/ml). Enzymatic activities of acid and alkaline phosphatase, aminopeptidases, esterase and lipase and phospholipase were detected in the C. glabrata isolates. The genetic diversity and antifungal susceptibility profiles of C. glabrata isolates were presented in this study. Continued surveillance and monitoring of the incidence and antifungal resistance in C. glabrata isolates is necessary.

Matched MeSH terms: Fluconazole
Fulltext In silico identification of novel tuberculosis drug targets in mycobacterium tuberculosis P450 enzymes by interaction study with azole drugs

Suresh Kumar

Malaysian Journal of Medicine and Health Sciences, 2020;16(101):24-30.
MyJurnal

Introduction: Tuberculosis (TB) is one of the utmost serious infectious diseases worldwide. The emergence of multi- drug resistance demands the development of better or new putative drug targets for tuberculosis. Recent studies sug- gest Mycobacterium tuberculosis cytochrome P450 enzymes as promising drug targets and azole drugs as potential inhibitors. Methods: Various computational tools, like Expasy Protparam, Swiss model, RaptorX and Phyre2 were used to analyze 12 Mycobacterium tuberculosis P450 enzymes and determine their three-dimensional structure. The structural validation was done through a Ramachandran plot using RAMPAGE server. The docking of P450 enzymes with azole drugs was done with autodock ver 4.2.6. Results: Based on sub-cellular localization prediction using CEL- LO tool, P450 enzymes CYP123A1, CYP132A1, CYP135A1, CYP136A1, CYP140A1, and CYP143A1 were predicted to be in the cytoplasm. Through structure assessment by Ramachandran plot, the best homology modelled proteins were docked with azole drugs like clotrimazole, croconazole, econazole, fluconazole, itraconazole, itraconazole, ketaconazole and micronazole by using autodock. By docking method it is identified that ketaconazole drug has a high affinity towards most of the mycobacterium P450 enzymes followed by the itrconazole drug. CYP123A1 enzyme is preferable as a drug target due to high binding affinity towards ketoconazole followed by CYP135A1, CYP140A1 enzymes. Conclusion: This study would help in identifying putative novel drug targets in Mycobacterium tuberculosis, which can lead to promising candidates for the optimization and development of novel anti-mycobac- terial agents.

Matched MeSH terms: Fluconazole
Fulltext A fatal case of rhinocerebral mucormycosis

Nurul Suhaili Kamarudin, Rosni Ibrahim, Nur Hanani Ahmad, Siti Norbaya Masri

Malaysian Journal of Medicine and Health Sciences, 2020;16(2):329-331.
MyJurnal

Rhinocerebral mucormycosis is a potentially fatal and progressive angioinvasive fungal infection. It is classically described in patients with uncontrolled diabetes mellitus and hematological malignancies. This report describes a case of progressive rhinocerebral mucormycosis in a patient with poorly controlled diabetes who was on prolonged prednisolone therapy for autoimmune kidney disease. The patient, who was a female, presented to hospital with headache, orbital pain and nasal bridge swelling. Black eschar on nasal mucosae was present on admission. Later, she was started on intravenous fluconazole for the diagnosis of fungal sinusitis. Subsequently, she developed intra- cerebral haemorrhage complicated with transtentorial herniation. Diagnosis of rhinocerebral mucormycosis was later observed by a laboratory finding and the treatment was changed to intravenous amphotericin B. However, the patient succumbed to her illness on the 6th day of hospitalisation. This report discusses the risk factors associated with rhinocerebral mucormycosis as well as the underlying pathogenesis. This report will also highlight the importance of early diagnosis and appropriate treatment for mucormycosis to improve prognosis in patients.

Matched MeSH terms: Fluconazole
Fulltext The Current Status of Feline Sporotrichosis in Malaysia

Siew HH

Nihon Ishinkin Gakkai Zasshi, 2017;58(3):E107-E113.
PMID: 28855477 DOI: 10.3314/mmj.17.014

Feline sporotrichosis has been reported in Malaysia since the 1990's. Since then, studies have revealed that clinical clade D, Sporothrix schenckii sensu stricto, of a single clonal strain is the most common cause of this disease in Malaysia. The prevalence of a single clonal strain from a clinical clade was never before reported in Asia in a specific geographical niche. This raises the possibility of a process of purifying selection and subsequent clonal proliferation. While agricultural practices may serve as the selective pressure, direct causality has yet to be established. Studies into the thermo-tolerability of the Malaysian clonal strain of S. schenckii sensu stricto revealed that a small minority of clinical isolates have the capacity to grow at 37℃, while the majority displayed low susceptibility to commonly used antifungals in clinical practice, such as itraconazole (ITZ) and terbinafine (TRB). Despite unestablished breakpoints, suspected resistance (MIC > 4 mg/mL) towards amphotericin B (AMB) and fluconazole (FLC) was recorded in the isolates. This explains the often lack of clinical response in feline patients treated with recommended doses of antifungals, including ITZ. Coupled with the potential zoonotic transmission to clients and veterinarians, protracted treatment period, and subsequent cost of treatment, prognosis of feline sporotrichosis is often regarded to be poor. The use of a higher dose of ITZ has been reported, and an adoption of this high-dose treatment regime is reported in this manuscript, with complete cure achieved in cases of recalcitrant and/or unresponsive feline sporotrichosis, which would otherwise be euthanized.

Matched MeSH terms: Fluconazole/pharmacology
Brain-Eating Amoebae: Silver Nanoparticle Conjugation Enhanced Efficacy of Anti-Amoebic Drugs against Naegleria fowleri

Rajendran K, Anwar A, Khan NA, Siddiqui R

ACS Chem Neurosci, 2017 12 20;8(12):2626-2630.
PMID: 29206032 DOI: 10.1021/acschemneuro.7b00430

The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.

Matched MeSH terms: Fluconazole/administration & dosage
Anti-Candida albicans biofilm activity by Cassia spectabilis standardized methanol extract: an ultrastructural study

Torey A, Sasidharan S

Eur Rev Med Pharmacol Sci, 2011 Aug;15(8):875-82.
PMID: 21845797

Candida (C.) albicans infection in its biofilm mode of growth has taken centre point with the increasing recognition of its role in human infections due to the development of resistance to the commonly used antibiotic or phenotypic adaptation within the biofilm. Hence, in this study the inhibitory effect of methanol extract of Cassia (C.) spectabilis leaves was evaluated against biofilm forming C. albicans.

Matched MeSH terms: Fluconazole/pharmacology
Itraconazole- and fluconazole-induced toxicity in rat hepatocytes: a comparative in vitro study

Somchit N, Hassim SM, Samsudin SH

Hum Exp Toxicol, 2002 Jan;21(1):43-8.
PMID: 12046723

This current study was to investigate the in vitro cytotoxicity of rat hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes. P450 content was reduced approximately 30% for both types of hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole was reduced significantly by phenobarbital pretreatment. Phenobarbital did not have any effect on the cytotoxicity induced by fluconazole. These results demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and fluconazole that were expressed in a dose- and time-dependent manner. Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.

Matched MeSH terms: Fluconazole/toxicity*
Fulltext Candida albicans infection of a prosthetic knee replacement: a case report

Badrul B, Ruslan G

Med J Malaysia, 2000 Sep;55 Suppl C:93-6.
PMID: 11200051

We report a 64 year old man who developed Candida albicans infection following total knee arthroplasty. A two-stage exchange arthroplasty was performed after an initial swab culture grew Acinobacter sp. A scanty growth of yeast was also found from the tissue culture. Intravenous cefuroxime was instituted for six weeks followed by reimplantation four months after the removal. Three weeks after that revision, the prosthesis became infected and a culture of knee aspirate established the diagnosis of Candida albicans infection. Treatment consisted of thorough debridement of the involved joint and oral fluconazole for a year. Infection was never totally resolved and a secondary infection with methicillin resistant staphylococcus aureus then developed. Excision arthroplasty was done at two and a half years after the initial infection. At five years follow-up the infection was quiescent and he had a range of movement of 30 degrees to 70 degrees. Knee brace was used to control the valgus-varus stability.

Matched MeSH terms: Fluconazole/therapeutic use
Cryptococcus humicolus meningitis: first case report in Malaysia

Ramli SR, Leong MC, Khaithir TM, Aziz MN, Loons LC, Rafia MH

Southeast Asian J. Trop. Med. Public Health, 2012 Sep;43(5):1212-7.
PMID: 23431829

We report a case of Cryptococcus humicolus meningitis complicated by communicating hydrocephalus in an apparently immunocompetent 49-year-old psychiatric patient from a nursing home. He presented with a history of poor oral intake, weight loss, headache, vomiting, blurred vision, frequent falls and unsteady gait for the previous three months. He had a history of chronic cough, productive of whitish sputum for the previous month but no hemoptysis. Cerebrospinal fluid culture was positive for Cryptococcus humicolus. He was treated with intravenous amphotericin B and oral fluconazole and had clinical and microbiological improvement after three weeks of treatment. Unfortunately, the patient acquired nosocomial methicillin-resistant Staphylococcus aureus infection and died due to overwhelming sepsis.

Matched MeSH terms: Fluconazole/therapeutic use
Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study

Somchit N, Norshahida AR, Hasiah AH, Zuraini A, Sulaiman MR, Noordin MM

Hum Exp Toxicol, 2004 Nov;23(11):519-25.
PMID: 15625777

Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.

Matched MeSH terms: Fluconazole/administration & dosage; Fluconazole/toxicity*
Idiopathic CD4+ T-lymphocytopenia in a child with disseminated cryptococcosis

Menon BS, Shuaib IL, Zamari M, Haq JA, Aiyar S, Noh LM

Ann Trop Paediatr, 1998 Mar;18(1):45-8.
PMID: 9692001

We describe a Malay girl with disseminated cryptococcosis affecting the lungs, liver, lymph nodes and bones. The diagnosis was made by culture of the bone marrow. Tests of immune function showed that she was HIV-negative but the CD4 percentage was persistently low. Idiopathic CD4+ T-lymphocytopenia was diagnosed. The child died despite two courses of anti-fungal therapy.

Matched MeSH terms: Fluconazole/therapeutic use
Recurrent candidaemia in a neonate with Hirschsprung's disease: fluconazole resistance and genetic relatedness of eight Candida tropicalis isolates

Chong PP, Chieng DC, Low LY, Hafeez A, Shamsudin MN, Seow HF, et al.

J Med Microbiol, 2006 Apr;55(Pt 4):423-428.
PMID: 16533990 DOI: 10.1099/jmm.0.46045-0

The incidence of candidaemia among immunocompromised patients in Malaysia is increasing at an alarming rate. Isolation of clinical strains that are resistant to fluconazole has also risen markedly. We report here the repeated isolation of Candida tropicalis from the blood of a neonatal patient with Hirschsprung's disease. In vitro fluconazole susceptibility tests of the eight isolates obtained at different time points showed that seven of the isolates were resistant and one isolate was scored as susceptible dose-dependent. Random amplification of polymorphic DNA fingerprinting of the isolates using three primers and subsequent phylogenetic analysis revealed that these isolates were highly similar strains having minor genetic divergence, with a mean pairwise similarity coefficient of 0.893+/-0.041. The source of the infectious agent was thought to be the central venous catheter, as culture of its tip produced fluconazole-resistant C. tropicalis. This study demonstrates the utility of applying molecular epidemiology techniques to complement traditional mycological culture and drug susceptibility tests for accurate and appropriate management of recurrent candidaemia and highlights the need for newer antifungals that can combat the emergence of fluconazole-resistant C. tropicalis strains.

Matched MeSH terms: Fluconazole/pharmacology*
Fulltext In vitro activity of fluconazole and voriconazole against clinical isolates of Candida spp. by E-test method

Madhavan P, Jamal F, Chong PP, Ng KP

Trop Biomed, 2010 Aug;27(2):200-7.
PMID: 20962716 MyJurnal

The in vitro susceptibility of clinical Candida isolates towards fluconazole and voriconazole was determined using the E-test method. A total of 41 clinical isolates recovered from patients since 2004 until 2009 from two local hospitals in Kuala Lumpur, Malaysia were used. These comprised Candida tropicalis, Candida albicans, Candida krusei, Candida parapsilosis, Candida rugosa, Candida dubliniensis and Candida glabrata. Strains from American Type Culture Collection were used as quality control. Lawn cultures of the isolates on RPMI-1640 agar medium supplemented with 2% glucose were incubated with the E-test strips at 35ºC for 48 h. Our results show that 71% were susceptible to fluconazole and 90% were susceptible to voriconazole. All strains of C. krusei were resistant to fluconazole and 50% were susceptible in a dose-dependent manner to voriconazole. There were 66% and 33% of C. glabrata that were resistant to fluconazole and voriconazole. Our study revealed that majority of the clinical Candida isolates was susceptible to fluconazole and voriconazole with a small percentage being resistant to both the drugs.

Matched MeSH terms: Fluconazole/pharmacology*
Comparative Study of the Effects of Fluconazole and Voriconazole on Candida glabrata, Candida parapsilosis and Candida rugosa Biofilms

Madhavan P, Jamal F, Pei CP, Othman F, Karunanidhi A, Ng KP

Mycopathologia, 2018 Jun;183(3):499-511.
PMID: 29380188 DOI: 10.1007/s11046-018-0243-z

Infections by non-albicans Candida species are a life-threatening condition, and formation of biofilms can lead to treatment failure in a clinical setting. This study was aimed to demonstrate the in vitro antibiofilm activity of fluconazole (FLU) and voriconazole (VOR) against C. glabrata, C. parapsilosis and C. rugosa with diverse antifungal susceptibilities to FLU and VOR. The antibiofilm activities of FLU and VOR in the form of suspension as well as pre-coatings were assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction assay. Morphological and intracellular changes exerted by the antifungal drugs on Candida cells were examined by scanning electron microscope (SEM) and transmission electron microscope (TEM). The results of the antibiofilm activities showed that FLU drug suspension was capable of killing C. parapsilosis and C. rugosa at minimum inhibitory concentrations (MICs) of 4× MIC FLU and 256× MIC FLU, respectively. While VOR MICs ranging from 2× to 32× were capable of killing the biofilms of all Candida spp tested. The antibiofilm activities of pre-coated FLU were able to kill the biofilms at ¼× MIC FLU and ½× MIC FLU for C. parapsilosis and C. rugosa strains, respectively. While pre-coated VOR was able to kill the biofilms, all three Candida sp at ½× MIC VOR. SEM and TEM examinations showed that FLU and VOR treatments exerted significant impact on Candida cell with various degrees of morphological changes. In conclusion, a fourfold reduction in MIC50 of FLU and VOR towards ATCC strains of C. glabrata, C. rugosa and C. rugosa clinical strain was observed in this study.

Matched MeSH terms: Fluconazole/pharmacology*
Fulltext Design, synthesis and therapeutic potential of 3-(2-(1H-benzo[d]imidazol-2-ylthio)acetamido)-N-(substituted phenyl)benzamide analogues

Tahlan S, Ramasamy K, Lim SM, Shah SAA, Mani V, Narasimhan B

Chem Cent J, 2018 Dec 19;12(1):139.
PMID: 30569392 DOI: 10.1186/s13065-018-0513-3

BACKGROUND: The emergence of bacterial resistance is a major public health problem. It is essential to develop and synthesize new therapeutic agents with better activity. The mode of actions of certain newly developed antimicrobial agents, however, exhibited very limited effect in treating life threatening systemic infections. Therefore, the advancement of multi-potent and efficient antimicrobial agents is crucial to overcome the increased multi-drug resistance of bacteria and fungi. Cancer, which remains as one of the primary causes of deaths and is commonly treated by chemotherapeutic agents, is also in need of novel and efficacious agents to treat resistant cases. As such, a sequence of novel substituted benzamides was designed, synthesized and evaluated for their antimicrobial and anticancer activities.
METHODOLOGY: All synthesized compounds were characterized by IR, NMR, Mass and elemental analysis followed by in vitro antimicrobial studies against Gram-positive (Staphylococcus aureus), Gram-negative (Salmonella typhi and Klebsiella pneumoniae) bacterial and fungal (Candida albicans and Aspergillus niger) strains by the tube dilution method. The in vitro anticancer evaluation was carried out against the human colorectal carcinoma cell line (HCT116), using the Sulforhodamine B assay.
RESULTS, DISCUSSION AND CONCLUSION: Compound W6 (MICsa, st, kp = 5.19 µM) emerged as a significant antibacterial agent against all tested bacterial strains i.e. Gram-positive (S. aureus), Gram-negative (S. typhi, K. pneumoniae) while compound W1 (MICca, an = 5.08 µM) was most potent against fungal strains (A. niger and C. albicans) and comparable to fluconazole (MIC = 8.16 µM). The anticancer screening demonstrated that compound W17 (IC50 = 4.12 µM) was most potent amongst the synthesized compounds and also more potent than the standard drug 5-FU (IC50 = 7.69 µM).

Matched MeSH terms: Fluconazole

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