Synthesis, Anticancer Activity, and In Silico Modeling of Alkylsulfonyl Benzimidazole Derivatives: Unveiling Potent Bcl-2 Inhibitors for Breast Cancer.

A series of alkylsulfonyl 1H-benzo[d]imidazole derivatives were synthesized and evaluated for anticancer activity against human breast cancer cells, MCF-7 in vitro. The cytotoxic potential was determined using the xCELLigence real-time cell analysis, and expression levels of genes related to microtubule organization, tumor suppression, apoptosis, cell cycle, and proliferation were examined by quantitative real-time polymerase chain reaction. Molecular docking against Bcl-2 was carried out using AutoDock Vina, while ADME studies were performed to predict the physicochemical and drug-likeness properties of the synthesized compounds. The results revealed that compounds 23 and 27 were the most potent cytotoxic derivatives against MCF-7 cells. Gene expression analysis showed that BCL-2 was the most prominent gene studied. Treatment of MCF-7 cells with compounds 23 and 27 resulted in significant downregulation of the BCL-2 gene, with fold changes of 128 and 256, respectively. Docking analysis predicted a strong interaction between the compounds and the target protein. Interestingly, all of the compounds exhibit a higher binding affinity toward Bcl-2 than the standard drug (compound 27 vina score = -9.6 kcal/mol, vincristine = -6.7 kcal/mol). Molecular dynamics simulations of compounds 23 and 27 showed a permanent stabilization in the binding site of Bcl-2 for 200 ns. Based on Lipinski and Veber's filters, all synthesized compounds displayed drug-like characteristics. These findings suggest that compounds 23 and 27 were the most promising cytotoxic compounds and downregulated the expression of the BCL-2 gene. These derivatives could be further explored as potential candidates for the treatment of breast cancer.

The use of Traditional Medicines for Sexual Enhancement in Northern Nigeria.

BACKGROUND: There is a paucity of information on the use of traditional medicine TM to improve sexual performance. This study aims to assess the prevalence and self-reported adverse effects associated with the use of TM as a sexual enhancer in northern Nigeria. METHODS: The study was a cross-sectional design among adults aged 18 years and above, who are residing in northern Nigeria. A mixed-mode approach was utilized using face-to-face interviews and an online survey. For the online survey, a link to the questionnaire was shared on the social media platforms of the targeted participants. RESULTS: A total of 794 eligible participants completed the survey over the six weeks. Of this number, 508 reported ever using TM for sexual enhancement, with a prevalence of 64% (95% CI: 60.5, 67.3). About 30 (3.8%) reported daily use, 49 (4.9%) weekly, 65 (8.2%) monthly and 473 (59.6%) as when needed. Islamic medicine was the most frequently implicated TM. Most respondents obtained it TM practitioners 213 (26.8%). Participants 164 (20.7%) reported experiencing side effects, mostly headaches 59 (35.9%), and 31 (3.9%) were severe (required hospitalization). Predictors of TM use for sexual enhancement were found to be gender, marital status, number of wives, ethnicity, educational level, and lifestyle. CONCLUSION: The use of TM for sexual enhancement is common among the adult population in northern Nigeria. One out of five of the users reported an adverse event. Therefore, there is a need for improved awareness of the safe use of the TM in the community, especially among females, those with multiple wives, a low education level, and poor lifestyles.

Cyclin-Dependent Kinase 4/6 Inhibitors Against Breast Cancer.

Breast cancer is the most frequently diagnosed and leading cause of cancer-related deaths in women worldwide. Based on global cancer (GLOBOCAN) 2020 statistics, 1 in 4 cancer cases and 1 in 6 cancer deaths are attributable to breast cancer, leading both in incidence and mortality. To address the increasing burden of cancer, novel therapeutic approaches that target key hallmarks of cancer are explored in cancer drug discovery. Cyclin-dependent kinase (CDK) inhibitors are generally purine and pyrimidine analogues validated for the treatment of cancer due to their unique roles in cancer deregulation and novel therapeutic potentials. So far, three orally administered, potent and highly selective CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) have been approved by the FDA for the targeted treatment of advanced or metastatic breast cancer in combination with endocrine therapy. Furthermore, several compounds derived from various synthetic scaffolds are being explored with promising results and positive outcomes in various stages of clinical trials. In this review, we highlight these CDK4/6 inhibitor compounds with potent anti-CDK4/6, in vitro and in vivo activities on breast cancer cells. With the remarkable prospects of these compounds, there is great optimism further novel CDK inhibitor compounds will be discovered in the future that could boost therapeutic options for cancer treatment.

Incorporation of Protecting Groups in Organic Chemistry: A Mini-Review.

The approach of utilizing protecting groups (PGs) in organic chemistry has led to the successful syntheses of an array of useful organic compounds. This strategy has also addressed some of the complexities associated with many organic reactions. These PGs find useful applications in simple and complex reactions that involve the synthesis of large organic compounds such as peptides, and oligosaccharides. The fundamental role of PGs is to prevent undesired reactions that could hinder the progress or completion of such reactions. Ideal PGs must be utilized in this regard to achieve the desired objectives. This review describes the diverse protecting groups found in the literatures, the functional moieties for the protection, deprotection strategies, and their relevant applications in organic synthesis.

Delayed Access to COVID-19 Vaccines: A Perspective on Low-income Countries in Africa.

The development of COVID-19 vaccines was a landmark in the current efforts to contain the global pandemic caused by the novel SARS-CoV-2. Consequently, vaccine rollout and inoculation campaigns continue to progress steadily across the globe. However, "skewed" rollout, or the inequitable or delayed access to the vaccines encountered particularly by low-income countries in Africa, remains a source of great concern. This may negatively affect the continent and could lead to increased transmission, travel restrictions, further economic disruptions, and increased morbidity and mortality. Ultimately, these negative consequences could directly or indirectly hamper global efforts to defeat the pandemic. Access to COVID-19 vaccines is a global priority and provides a source of hope to bring the pandemic under control. High-income nations, national governments, donor agencies, and other relevant stakeholders must support the World Health Organization's COVAX initiative to ensure fair, rapid and equitable distribution of the vaccines to countries, irrespective of income level. This effort will rapidly bring the pandemic under control and impact the recovery of the global economy. Low-income nations in Africa must significantly invest in research, health care, vaccines, and drug development and must remain proactive in preparing against future pandemics. This review examines the rollout of the COVID-19 vaccines with a focus on Africa.

Preclinical efficacy of African medicinal plants used in the treatment of snakebite envenoming: a systematic review protocol.

BACKGROUND: Snakebite envenoming (SBE) is a high-priority, neglected, tropical disease that affects millions of people in developing countries annually. The only available standard drug used for the treatment of SBE is antisnake venom (ASV) which consists of immunoglobulins that have been purified from the plasma of animals hyper-immunized against snake venoms. The use of plants as alternatives for treatment of poisonous bites particularly snakebites is important in remote areas where there might be limited, or no access to hospitals and storage facilities for antivenom. The pharmacological activity of some of the medicinal plants used traditionally in the treatment of SBE have also been scientifically validated. METHOD: A systematic review will be conducted according to the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies checklist for study quality in animal/in vivo studies. The tool will be modified and validated to assess in vitro models and studies that combine in vivo and in vitro studies. The systematic review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. English published articles on African medicinal plants used in the treatment of snakebite envenoming will be searched in Medline, Embase, and Scopus from 2000 to 2021. DISSEMINATION: The findings of the study will be communicated through publication in peer-reviewed journal and presentation at scientific conferences. Medicinal plants have been important sources for the development of many effective drugs currently available in orthodox medicine. Botanically derived medicines have played a major role in human societies throughout history. Plants components used in traditional medicine gained much attention by many toxinologists as a tool for designing potent antidotes against snake envenoming. Our systematic review will provide a synthesis of the literature on the efficacy of these medicinal plants. We will also appraise the prospects of African medicinal plants with pharmacologically demonstrated activity against snakebite and envenoming.