As the circular supply chain (CSC) gains traction in literature and practice, some academic groups are developing new fields that proceed from the CSC as a precisely technical concept. In order to examine the trends of CSC over time, to define how previous researchers have conceptualized the CSC ideology, and to identify the barriers to CSC adoption in businesses operations. This systematic review of the literature (n = 55) examines and discusses the disparate body of knowledge on supply chains (SCs). The paper claims that there are still differences across the circular economy (CE) definitions because of alleged antecedents and scopes, which has led to several research streams. However, CSC's goal remained the same: to encourage sustainable strategies that rejected the traditional linear paradigm that had harmed the environment. In order to be included in future practices and approaches, eight significant, interdisciplinary issues were discovered using SLR, along with the corresponding sub-challenges. These difficulties were discussed in this paper. Aiming to address the current concerns about balancing the environmental and economic perspectives, this study will provide guidelines to future researchers to identify the challenges from a real-world point of view by taking into account the social, environmental, and economic perspectives altogether.
We report one-pot synthesis of a series of new 3-aryl-8-methylquinazolin-4(3H)-ones (QNZ) and their antimicrobial activity against Acanthamoeba castellanii belonging to T4 genotype. A library of fifteen synthetic derivatives of QNZs was synthesized, and their structural elucidation was performed by using nuclear magnetic resonance (NMR) spectroscopy and electron impact mass spectrometry (EI-MS). Elemental analyses and high-resolution mass spectrometry data of all derivatives were found to be in agreeable range. Amoebicidal assays performed at concentrations ranging from 50 to 100 μg/mL revealed that all derivatives of QNZ significantly decreased the viability of A. castellanii and QNZ 2, 5, 8, and 13 were found to have efficient antiamoebic effects. Field emission scanning electron microscopy (FESEM) imaging of amoeba treated with compounds 5 and 15 showed that these compounds cause structural alterations on the walls of A. castellanii. Furthermore, several QNZs inhibited the encystation and excystationas as well as abolished A. castellanii-mediated host cells cytopathogenicity in human cells. Whereas, these QNZs showed negligible cytotoxicity when tested against human cells in vitro. Hence, this study identified potential lead molecules having promising properties for drug development against A. castellanii. A brief structure-activity relationship is also developed to optimize the hit of most potent compounds from the library. To the best of our knowledge, it is first of its kind medicinal chemistry approach on a single class of compounds i.e., quinazolinone against keratitis and brain infection causing free-living amoeba, A. castellanii.
Naegleria fowleri and Balamuthia mandrillaris are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents. To study the antiamoebic activity of these synthetic arylquinazolinones, amoebicidal and amoebistatic assays were performed against N. fowleri and B. mandrillaris. Moreover, amoebae-mediated host cells cytotopathogenicity and cytotoxicity assays were performed against human keratinocytes cells in vitro. The results revealed that selected arylquinazolinones derivatives decreased the viability of B. mandrillaris and N. fowleri significantly (P < 0.05) and reduced cytopathogenicity of both parasites. Furthermore, these compounds were also found to be least cytotoxic against HaCat cells. Considering that nanoparticle-based materials possess potent in vitro activity against brain-eating amoebae, we conjugated quinazolinones derivatives with silver nanoparticles and showed that activities of the drugs were enhanced successfully after conjugation. The current study suggests that quinazolinones alone as well as conjugated with silver nanoparticles may serve as potent therapeutics against brain-eating amoebae.
Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1-19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 μg/mL. The IC50 was found to be between 100 and 50 μg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii-mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii.
Drucker's knowledge-worker productivity theory and knowledge-based view of the firm theory are widely employed in many disciplines but there is little application of these theories in knowledge-based innovation among academic researchers. Therefore, this study intends to evaluate the effects of the knowledge management process on knowledge-based innovation alongside with mediating role of Malaysian academic researchers' productivity during the Pandemic of COVID-19. Using a random sampling technique, data was collected from 382 academic researchers. Questionnaires were self-administered and data was analyzed via Smart PLS-SEM. Knowledge management process and knowledge workers' productivity have a positive and significant relationship with the knowledge-based innovation among academic researchers during the Pandemic of COVID-19. In addition, knowledge workers' productivity mediates the relationship between the knowledge management process (knowledge creation, knowledge acquisition, knowledge sharing, and knowledge utilization) and knowledge-based innovation during the Pandemic of COVID-19. Results have also directed knowledge sharing as the key factor in knowledge-based innovation and a stimulating task for management discipline around the world during the Pandemic of COVID-19. This study provides interesting insights on Malaysian academic researchers' productivity by evaluating the effects of knowledge creation, acquisition, sharing, and application on the knowledge-based innovation among academic researchers during the Pandemic of COVID-19. These useful insights would enable policymakers to develop more influential educational strategies. By assimilating the literature of defined variables, the main contribution of this study is the evaluation of knowledge creation, acquisition, sharing, and utilization into knowledge-based innovation alongside the mediating role of knowledge workers productivity in the higher education sector of Malaysia during the Pandemic of COVID-19.