Challenges and Recent Advances of Novel Chemical Inhibitors in Medulloblastoma Therapy.

Medulloblastoma is a common term used for the juvenile malignant brain tumor, and its treatment is exciting due to different genetic origins, improper transportation of drug across the blood-brain barrier, and chemo-resistance with various side effects. Currently, medulloblastoma divided into four significant subsections (Wnt, Shh, Group 3, and Group 4) is based on their hereditary modulation and histopathological advancement. In this chapter, we tried to combine several novel chemical therapeutic agents active toward medulloblastoma therapy. All these compounds have potent activity to inhibit the medulloblastoma.

Natural Thiazoline-Based Cyclodepsipeptides from Marine Cyanobacteria: Chemistry, Bioefficiency and Clinical Aspects.

BACKGROUND: Peptides and peptide-based therapeutics are biomolecules that demarcate a significant chemical space to bridge small molecules with biological therapeutics, such as antibodies, recombinant proteins, and protein domains. INTRODUCTION: Cyclooligopeptides and depsipeptides, particularly cyanobacteria-derived thiazoline-based polypeptides (CTBCs), exhibit a wide array of pharmacological activities due to their unique structural features and interesting bioactions, which furnish them as promising leads for drug discovery. METHODS: In the present study, we comprehensively review the natural sources, distinguishing chemistries, and pertinent bioprofiles of CTBCs. We analyze their structural peculiarities counting the mode of actions for biological portrayals which render CTBCs as indispensable sources for emergence of prospective peptide-based therapeutics. In this milieu, metal organic frameworks and their biomedical applications are also briefly discussed. To boot, the challenges, approaches, and clinical status of peptide-based therapeutics are conferred. RESULTS: Based on these analyses, CTBCs can be appraised as ideal drug targets that have always remained a challenge for traditional small molecules, like those involved in protein- protein interactions or to be developed as potential cancer-targeting nanomaterials. Cyclization-induced reduced conformational freedom of these cyclooligopeptides contribute to improved metabolic stability and binding affinity to their molecular targets. Clinical success of several cyclic peptides provokes the large library-screening and synthesis of natural product-like cyclic peptides to address the unmet medical needs. CONCLUSION: CTBCs can be considered as the most promising lead compounds for drug discovery. Adopting the amalgamation of advanced biological and biopharmaceutical strategies might endure these cyclopeptides to be prospective biomolecules for futuristic therapeutic applications in the coming times.

Microbiome and host crosstalk: A new paradigm to cancer therapy.

The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.

Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects.

Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide-peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents.

Synthesis of newer 1,2,3-triazole linked chalcone and flavone hybrid compounds and evaluation of their antimicrobial and cytotoxic activities.

The present study was carried out in an attempt to synthesize a new class of antimicrobial and antiplasmodial agents by copper catalyzed click chemistry to afford 25 compounds 10-14(a-e) of 1,4-disubstituted-1,2,3-triazole derivatives of chalcones and flavones. The structures of the newly synthesized compounds were established by elemental analysis, IR, (1)H NMR, (13)C NMR and Mass spectral data. The newly synthesized compounds were evaluated for their antibacterial activity against Gram positive bacteria (Staphylococcus aureus, Enterococcus faecalis), Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Shigella boydii, Klebsiella pneumoniae) and antifungal activity against (Candida albicans, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Dermatophyte) as well as molds (Aspergillus niger, Aspergillus fumigatus). The antiplasmodial and cytotoxic activities of these compounds were also evaluated against human malaria parasite Plasmodium falciparum strain 3D7 and human hepato-cellular carcinoma cells (Huh-7), respectively. Compounds 10a, 10c, 10d, 12c and 14e showed promising antibacterial activity while compounds 10e, 11d, 11e, 12c, 13a, 13b, 13e, 14a and 14d showed good antifungal activity as compared to the corresponding standard drugs. Compound 10b was found to be the most active against Plasmodium falciparum while the remaining compounds showed moderate to weak antiplasmodial activity. However, cytotoxic activities of all compounds were found ineffective against Huh-7 cells.

Neurocysticercosis and its impact on crude prevalence rate of epilepsy in an Indian community.

BACKGROUND: Community-based studies of epilepsy in India have reported variable prevalence rates, 5-10/1000 population. Reasons for this wide variation in the prevalence rates are uncertain. Most of the earlier studies had not done appropriate investigations to establish the possible etiology. AIM: To study the prevalence and etiological profile of active epilepsy in the rural population of Uttarakhand. MATERIAL AND METHODS: In this rural community-based study in the state of Uttarakhand, a door-to-door survey was conducted using validated questionnaire. All the suspected cases of epilepsy were examined by a neurologist to confirm the diagnosis of epilepsy and all the confirmed cases underwent contrast computed tomography (CT) scan and electroencephalography (EEG). Epilepsy and epilepsy syndromes were classified using the classifications proposed by the International League Against Epilepsy. RESULTS: Of the 14,086 population studied, 141 cases of active epilepsy were detected giving a crude prevalence rate of 1%. After clinical evaluation and scanning, 35 (24.8%) were found to have seizure disorder active neurocysticercosis (NCC) and 14 (9.9%) had remote symptomatic seizures related to calcified granuloma. After excluding acute and remote symptomatic cases related to NCC, prevalence rate of epilepsy was 6.5/1000. CONCLUSION: The study suggests that the region-specific prevalence rates of epilepsy in India are partly dependent on the prevalence of NCC in the given community. To some extent, this may be responsible for variable rates of epilepsy prevalence reported from different regions of the country.

Oxidants and ocular tumors.

Serum superoxide dismutase and catalase assays were performed using spectrophotometry in 60 adults and children with benign or malignant tumors and in controls. There was a statistically significant difference in the antioxidative status of children with intraocular tumors (primary retinoblastoma) compared with children without tumors. The difference was not significant in adults. These enzymes may be of value in the early diagnosis of malignant intraocular tumor, especially retinoblastoma.

'Quick course' neoadjuvant chemotherapy with cisplatin, bleomycin and vincristine in advanced cervical cancer.

To evaluate the response and safety of 'quick course' neoadjuvant chemotherapy, 30 patients with advanced squamous cell carcinoma of cervix were given cisplatin, bleomycin, and vincristine weekly for 3 courses. The response was evaluated by subjective parameters and by standard response criteria. In addition to the marked improvement in symptoms, the overall objective response was 60% with a complete pathological response of 6.6%. Tumor volume decreased significantly (p=0.002) after chemotherapy. Patients with stage IB and 27% (3 of 11) of patients with stage II disease who became technically stage IB (stage reduction) after chemotherapy underwent surgery. Radiotherapy was given to the remaining patients. All patients tolerated the chemotherapy.