Mini Reviews in Medicinal Chemistry - Volume 23, Issue 10, 2023

Multidrug Resistance (MDR) in tumor cells, a phenomenon in which tumor cells become resistant to chemotherapeutic drugs with different chemical structures and mechanisms of action, is a major obstacle to tumor therapy and is an urgent problem to be addressed. Autophagy, widely found in eukaryotic cells, is a lysosome-dependent pathway of self-degradation. In different environments, autophagy can play different roles in the self-protection of cells. At different stages of tumorigenesis, autophagy can play two distinct roles: inhibition of cancer and promotion of cancer. The relationship between autophagy and drug resistance in tumor cells is complex. Moreover, autophagy can play a role in promoting drug resistance and drug sensitivity through different molecular pathways. This study aimed to investigate the relationship between autophagy and drug resistance in tumor cells from the perspective of molecular mechanisms.

It is estimated that viral infections contribute 15-20% of all human cancers. Several types of human papillomaviruse (HPV) are related to the development of many cancer types and their treatment. About 200 HPV viruses have been identified, and each type of virus is integrated with a certain type of clinical lesions affecting the areas of skin and mucous membranes. Infections associated with HPV are known to cause multiple cancer types such as uterine cancer, cervical, vaginal carcinoma, and other varieties of carcinomas such as genital and oropharyngeal, penile, and short-lived carcinomas. Most of the HPV types are considered as high-risk mutants that can provoke cervical cancer in females in addition to significant contribution to other cancer types such as anogenital cancer and tumor in head and neck regions. Among them, high risk human papilloma viruses (HR-HPV) subtypes 16 and 18 play a major role in the etiology of cervical cancer worldwide. Although, cervical cancer incidence and fatality rates vary greatly depending on geographical area, it is the leading cause of mortality in women around the world. In addition, it is epidemiologically similar to a sexually transmitted disease of low infectivity. In this review article, the association of HPV with different types of cancers have been explained, but the main focus remains on cervical cancer.

Selenium (Se), a semi-metallic element, has chemical properties similar to sulfur; however, it has comparatively low electronegativity as well as a large atomic radius than sulfur. These features bestow selenium-containing compounds with extraordinary reactivity, sensitivity, and potential for several applications like chemical alteration, protein engineering, chemical (semi)synthesis, etc. Organoselenium chemistry is emerging fastly, however, examples of effective incorporation of Se into the peptides are relatively scarce. Providentially, there has been a drastic interest in synthesizing and applying selenoproteins and selenium-containing peptides over the last few decades. In this minireview, the synthetic methodologies of selenium-containing peptides and a brief description of their chemistry and biological activities are summarized. These methodologies enable access to various natural and unnatural selenium-containing peptides that have been used in a range of applications, from modulating protein characteristics to structure-activity relationship (SAR) studies for applications in nutraceuticals and drug development. This review aims at the audience interested in learning about the synthesis as well as will open new dimensions for their future research by aiding in the design of biologically interesting selenium-containing peptides.

The application of privileged structures in drug design is an effective strategy, which usually leads to innovative hits/leads and successful structural optimization. Pyrrolo[2, 3- d]pyrimidine are such a scaffold which are frequently used in many clinical drugs. The biocompounds bearing pyrrolo[2, 3-d]pyrimidine skeleton show different pharmacological effects such as anti-neurodegenerative, anti-inflammatory, antibacterial, and antitumor activities. In this article, we reviewed the representative structures and biological characteristics of reported synthetic pyrrolo[2, 3-d]pyrimidine compounds from 2017 to 2021. The linked diseases and targets were also mentioned briefly. This work might provide a reference for the subsequent drug discovery based on pyrrolo[2, 3-d]pyrimidine scaffold.

Background: The chemotherapy modality is generally used for treating colorectal cancer. However, the clinical application of chemotherapeutic drugs may be limited due to their adverse effects on normal cells/tissues and the development of cancer resistance. Using the combined treatment of chemotherapy drugs and natural bioactive compounds (such as resveratrol) can alleviate adverse drug reactions and induce synergies between the drugs. Objective: In the current review, the potential therapeutic impacts of resveratrol during colorectal cancer chemotherapy were studied. Methods: Based on the PRISMA guideline, we performed a systematic search in different electronic databases up to May, 2021. Following the search, 321 papers were found and then screened for eligibility. Twenty-seven papers were finally included in the present study Results: Compared to the control group, the growth inhibition of cancerous cells treated with chemotherapeutic drugs was considerably higher, and resveratrol co-administration synergistically increased chemotherapy-induced cytotoxicity. Moreover, a reduction in the tumor weight, volume and growth of mice was observed following chemotherapy administration compared to the untreated groups, and these reductions were predominant in animals treated with resveratrol plus chemotherapy. Other findings showed that chemotherapy alone and in combination with resveratrol modulated the cell cycle profile of cancerous cells. Furthermore, chemotherapy treatment induced a set of biochemical and histopathological alterations in cancer cells/tissues, and these changes were synergized following resveratrol co-treatment (in most of the cases), excluding inflammatory mediators. Conclusion: In most cases, resveratrol co-administration could sensitize cancerous cells to chemotherapy drugs through its oxidant, apoptosis, anti-inflammatory activities, etc. Nevertheless, suggesting the use of resveratrol during chemotherapy of colorectal cancer patients requires further clinical studies.