Anticancer Functions of Pyridine Heterocycles

Pyridine is a heterocyclic molecule with a nitrogen atom that is often found in nature. As a prosthetic group taking part in redox processes in the biological system, it plays an important function in many enzymes of the living system. Pyridine is an important pharmacophore, a privileged scaffold, and a superior heterocyclic system in drug development, with various applications in anticancer research because of its ability to work on significant receptors. Typically, it is the core of several currently available medicines. In the fight against cancer, many pyridine derivatives have been shown to inhibit kinases, androgen receptors, tubulin polymerization, topoisomerase enzyme, human carbonic anhydrase, and several other targets. Researchers are now concentrating on developing pyridine novel entities with other moieties for cancer therapy. This section presents pyridine derivative synthesis and biological expansions, as well as their target receptor sites

Microbiology of Urinary Tract Infections in Gaborone, Botswana

Objective The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns. Methods This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available. Results A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of E. coli isolates to ampicillin and co-trimoxazole was greater than 60% in all settings. HIV status did not significantly impact the microbiology of UTIs, but did impact antimicrobial resistance to co-trimoxazole. Conclusions Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging. Ampicillin, co-trimoxazole, and ciprofloxacin should not be used as empiric treatment for UTI in this context. Nitrofurantoin could be used for simple cystitis; aminoglycosides for uncomplicated UTI in inpatients

Collision of Three Pandemics: The Coexistence of Cervical Cancer, HIV Infection, and Prior Tuberculosis in the Sub-Saharan Country of Botswana.

Cervical cancer is the leading cause of cancer-related mortality in the developing world, where HIV and Mycobacterium tuberculosis (TB) infection are also endemic. HIV infection is independently associated with increased morbidity and mortality among women with cervical cancer. TB is believed to increase the risk of malignancies and could cause chronic inflammation in the gynecologic tract. However, the relationship between cervical cancer and TB in settings hyperendemic for HIV is unknown. We found that 18 (10%) of a cohort of 180 women with cervical cancer in Botswana had a history of TB disease. Age and HIV infection were also associated with a history of TB disease. Our data show that prior TB disease is highly prevalent among patients with cervical cancer infected with HIV. The coexistence of cervical cancer, HIV infection, and prior TB infection might be higher than expected in the general population. Prospective studies are needed to better determine the impact of the collision of these three world health epidemics

Breast Cancer and HIV in Sub-Saharan Africa: A Complex Relationship

Introduction: The number and lifespan of individuals living with HIV have increased significantly with the scale-up of antiretroviral therapy. Furthermore, the incidence of breast cancer in women with HIV is growing, especially in sub-Saharan Africa (SSA). However, the association between HIV infection and breast cancer is not well understood. Methods: A literature search was performed to identify articles published in journals pertaining to breast cancer and HIV, with an emphasis on SSA. Selected US-based studies were also identified for comparison. Results: Among the 56 studies reviewed, the largest study examined 314 patients with breast cancer and HIV in the United States. There is no consensus on whether HIV infection acts as a pro-oncogenic or antioncogenic factor in breast cancer, and it may have no relation to breast cancer. A higher incidence of breast cancer is reported in high-income countries than in SSA, although breast cancer in SSA presents at a younger age and at a more advanced stage. Some studies show that patients with breast cancer and HIV experience worse chemotherapy toxicity than do patients without HIV. Data on treatment outcomes are limited. The largest study showed worse treatment outcomes in patients with HIV, compared with their counterparts without HIV. Conclusion: HIV infection has not been associated with different clinical presentation of breast cancer. However, some evidence suggests that concurrent diagnosis of HIV with breast cancer is associated with increased therapy-related toxicity and worse outcomes. Systematic prospective studies are needed to establish whether there is a specific association between breast cancer and HIV

Two biologically active thiophene-3-carboxamide derivatives

The crystallographic properties and intermolecular interactions in two biologically active thiophene-3-carboxamide derivatives were investigated. The two compounds, C 23H 25N 3OS and C 25H 27N 3OS show antibacterial and antifungal activities. The packing of the two compounds were stabilized through weak van der Waals forces. A significant intramolecular N-H···N hydrogen-bonding interaction in each structure was observed, which locks the molecule into a rigid pseudo-six-membered ring conformation and removes the conformational flexibility

Two biologically active thiophene-3-carboxamide derivatives

$The\hspace{5mm}two\hspace{5mm}title\hspace{5mm}compound,$ 2-(\lbrace (1Z)-[4-(dimethylamino)-phenyl]methylene\rbrace amino)-4,5-dimethyl-N-(2-methylphenyl)thiophene-3-carboxamide},\hspace{5mm}C_{23}H_{25}N_{3}OS,\hspace{5mm}(I),\hspace{5mm}and\hspace{5mm}2- \lbrace ((1E)-[4-(dimethylamino)phenyl \rbrace methylene}amino)-N-(4-methylphenyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide,\hspace{5mm}C_{25}H_{27}N_{3}OS, (II), show antibacterial and antifungal activities. The asymmetric unit of (II) contains two crystallographically independent molecules. The o-toluidine ring in (I) lies gauche with respect to the thiophene ring. In (II), the p-toluidine ring is coplanar with the thiophene ring in one molecule, but is tilted from it in the other molecule. Neither structure exhibits any significant intermolecular interactions, but in both, an intramolecular $N-H{\cdot\cdot\cdot}N$ hydrogen bond forms a pseudo-six-membered ring, thus locking the molecular conformation and removing conformational flexibility

Molecular detection of human papillomavirus (HPV) in highly fragmented DNA from cervical cancer biopsies using double-nested PCR

Archived Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimens can be a valuable source of human papillomavirus (HPV) nucleic acids for molecular biological analyses in retrospective studies. Although successful amplification with polymerase chain reaction (PCR) is essential for analysis of HPV DNA extracted from cervical FFPE specimens, extensive DNA damage due to cross-linking and fragmentation results in poor yield. Therefore, techniques to improve the diagnostic rate and sensitivity from FFPE tissues through PCR is highly desired and of wider interest. To overcome this, a highly sensitive double-nested PCR methodology was designed and optimized for limited-resource laboratories coupled with an organic extraction of DNA. This method allows the detection of a broad range of HPV genotypes and also allowing the sequencing of the final amplicon. Validation of the new approach developed was done with an automated DNA extraction coupled with Real Time PCR. Results showed that the proposed method achieves 96.3% of HPV detection as compared to 100% Abbott m2000rt used as ‘gold standard’. Moreover, the concordance rate between the two methods was equal for detecting HPV -16 or -18 genotypes. Nevertheless, the newly introduced assay has an advantage of: • Simultaneously identifying broad range of HPV genotypes besides HPV-16 and -18 from clinical samples. • It is an easy and cost-effective method that can be beneficial in resource-limited setting and can be employed for various molecular applications. • The method is indicated for highly degraded FFPE samples. Method name: Double-nested PCR for detecting and genotyping HPV, Keywords: HPV, FFPE, DNA, Double-nested PCR, RFLP, DNA sequencin

Multidisciplinary Gynecologic Oncology Clinic in Botswana: A Model for Multidisciplinary Oncology Care in Low- and Middle-Income Settings

Purpose Cervical cancer is a major cause of mortality in low- and middle-income countries (LMICs) and the most common cancer diagnosed in women in Botswana. Most women present with locally advanced disease, requiring chemotherapy and radiation. Care co-ordination requires input from a multidisciplinary team (MDT) to deliver appropriate, timely treatment. However, there are limited published examples of MDT implementation in LMICs. Methods: In May 2015, a weekly MDT clinic for gynecologic cancer care was initiated at Botswana’s national referral facility. The MDT clinic served as a forum for discussion and coordination of patients with gynecologic cancer and consisted of a gynecologist, pathologist, medical oncologist, radiation oncologist, palliative care specialist, and nurse coordinator. Results: Between May 2015 and December 2015, 135 patients were seen in the MDT clinic. The mean age of the patients was 49 years. Most (60%) of the patients were HIV positive. The most common diagnosis was cervical cancer (60%), followed by high-grade cervical intraepithelial neoplastic lesions (12%) and vulvar cancer (11%). Only data up to September 2015 were assessed for treatment delays. It was found that only 38% of patients needed more than one visit for care coordination before treatment initiation. Among patients with cervical cancer, the median delay from date of biopsy to start of radiation treatment was 39 days (interquartile range, 34 to 57 days) for patients treated after MDT initiation, compared with 108 days (interquartile range, 71 to 147 days) for patients treated before MDT initiation (P < .001). Conclusion: Implementation of MDT clinics in LMICs is feasible and can help reduce delays in treatment initiation, as demonstrated by a gynecologic MDT clinic in Botswana. Streamlining care through MDT clinics can enhance care coordination and improve clinical outcomes. This model can apply to cancer care in other LMICs

Human papillomavirus genotypes in women with invasive cervical cancer with and without human immunodeficiency virus infection in Botswana

Cervical cancer remains a significant cause of morbidity and mortality in women worldwide and is the leading cause of cancer-related death in Botswana. It is well established that women with HIV have a higher risk of persistent HPV infection leading to cervical cancer. We assessed HPV prevalence and genotype distribution in 126 tissue specimens from confirmed invasive cervical cancer cases using Abbott real-time PCR assay. Overall, 88 (69.8%) women were HIV-infected. Fifty-seven (64.8%) of the HIV-infected women had a baseline CD4+ count ≥350 cells/μl, and 82 (93.2%) were on antiretroviral therapy at the time of cervical cancer diagnosis. The median age of HIV-infected patients was significantly younger than that of HIV-uninfected patients (p &lt; 0.001). HPV DNA was detected in all of 126 (100%) of tissues analyzed in our study. The HPV genotypes identified included the HPV-16 (75.4%), HPV-18 (28.6%) and other high-risk (hr) HPV genotypes (16.7%). HIV infection was positively associated with the presence of the HPV-16 genotype (p = 0.036), but not with HPV-18 or with other high-risk (hr)-HPV genotypes. Thirty-three percent of the patients had multiple hr-HPV genotypes, with higher rates in HIV-infected women. These results highlight the importance and potential impact of large-scale HPV vaccination programs covering HPV-16 and HPV-18 genotypes in countries like Botswana with high burden of HIV infection