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Papers by José Augusto Pereira
![Research paper thumbnail of Determination of the Absolute Configuration of Bioactive Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones and Study of Their In Vitro Metabolic Profile](https://attachments.academia-assets.com/79368289/thumbnails/1.jpg)
](Molecules, 2021
In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug ... more In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyrazino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respectively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (-)-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1...
Biosystems, 2014
Theoretical models designed to test the metabolism-first hypothesis for prebiotic evolution have ... more Theoretical models designed to test the metabolism-first hypothesis for prebiotic evolution have yield
strong indications about the hypothesis validity but could sometimes use a more extensive identification
between model objects and real objects towards a more meaningful interpretation of results. In an
attempt to go in that direction, the string-based model SSE (“steady state evolution”) was developed,
where abstract molecules (strings) and catalytic interaction rules are based on some of the most
important features of carbon compounds in biological chemistry. The system is open with a random
inflow and outflow of strings but also with a permanent string food source. Although specific catalysis is a
key aspect of the model, used to define reaction rules, the focus is on energetics rather than kinetics.
Standard energy change tables were constructed and used with standard formation reactions to track
energy
flows through the interpretation of equilibrium constant values. Detection of metabolic networks
on the reaction system was done with elementary
flux mode (EFM) analysis. The combination of these
model design and analysis options enabled obtaining metabolic and catalytic networks showing several
central features of biological metabolism, some more clearly than in previous models: metabolic
networks with stepwise synthesis, energy coupling, catalysts regulation, SN2 coupling, redox coupling,
intermediate cycling, coupled inverse pathways (metabolic cycling), autocatalytic cycles and catalytic
cascades. The results strongly suggest that the main biological metabolism features, including the
genotype–phenotype interpretation, are caused by the principles of catalytic systems and are prior to
modern genetic systems principles. It also gives further theoretical support to the thesis that the basic
features of biologic metabolism are a consequence of the time evolution of a random catalyst search
working on an open system with a permanent food source. The importance of the food source
characteristics and evolutionary possibilities are discussed.
Proceedings of the 12th Portuguese Conference on Artificial Inteligence, 2005
A computational artificial chemistry (AC) system, called LAC, was developed bearing in mind the m... more A computational artificial chemistry (AC) system, called LAC, was developed bearing in mind the major biochemistry principles. Basic elements may be interpreted as small carbon molecules capable of bonding by nucleophilic substitution or nucleophilic addition. Reactions similar to hydrolysis and oxidation-reduction complete the present set of LAC site interaction rules. Reaction extension is governed by artificial thermodynamic principles and the reaction rate is controlled by specific catalysts made of the same kind of basic elements they act upon. The preliminary results of LAC experiments show the ability to mimic enzyme regulation and oscillatory reactions.
Book Reviews by José Augusto Pereira
Some of the ideas on this paper were presented at session #1, October 28th 2014 on the meeting "... more Some of the ideas on this paper were presented at session #1, October 28th 2014 on the meeting
" 'What Is Life?' – talks between the sciences and the humanities" celebrating the 70 years of Erwin Schrödinger's "What Is Life?" publication.
Abstracts by José Augusto Pereira
Biological carbon chemistry is formalized as a logical system, with a formal language, a grammar ... more Biological carbon chemistry is formalized as a logical system, with a formal language, a grammar and an inference system. The evolution of the language by random application of production rules yields sentence networks containing cycles due to grammar ambiguity. This suggests that any real chemistry that is a model of this type of formal system is able to develop chemical organizations.
Drafts by José Augusto Pereira
The linguistic description is proposed as the centrepiece of scientific modelling, being the way ... more The linguistic description is proposed as the centrepiece of scientific modelling, being the way by which the concepts that are considered relevant to a target system's composition and behaviour are presented, manipulated and communicated. The expression " model prescription " is used to mean the linguistic piece that describes a target system and consequently prescribes the production of synthetic data intended to model physically acquired data. The model prescription is in itself a concept of a target system that uses other systems' concepts, as well as concepts of objects, properties, relations and actions, to describe its structure and behaviour. The communication of a model prescription is therefore dependent on the intersubjective understanding and acceptance of the concepts used. Disentangled and narrower concepts of model and graphics are proposed. " Model " is restricted to representation by the same kind, categorically matched, while representations by different kind are named " graphics ". Data is identified as the sole touching point between physical systems and its human conceptualizations and the use of data-based inference by regression is analysed and some problems identified. Besides logic-mathematical relations, causal relations are an important part of modelling and a strict characterization of causal mechanisms is made based on energy transfers. Modelling examples are given to illustrate the generality of the definitions used as well as some of the problems with scientific modelling.
Molecules, 2021
In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug ... more In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyrazino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respectively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (-)-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1...
Biosystems, 2014
Theoretical models designed to test the metabolism-first hypothesis for prebiotic evolution have ... more Theoretical models designed to test the metabolism-first hypothesis for prebiotic evolution have yield
strong indications about the hypothesis validity but could sometimes use a more extensive identification
between model objects and real objects towards a more meaningful interpretation of results. In an
attempt to go in that direction, the string-based model SSE (“steady state evolution”) was developed,
where abstract molecules (strings) and catalytic interaction rules are based on some of the most
important features of carbon compounds in biological chemistry. The system is open with a random
inflow and outflow of strings but also with a permanent string food source. Although specific catalysis is a
key aspect of the model, used to define reaction rules, the focus is on energetics rather than kinetics.
Standard energy change tables were constructed and used with standard formation reactions to track
energy
flows through the interpretation of equilibrium constant values. Detection of metabolic networks
on the reaction system was done with elementary
flux mode (EFM) analysis. The combination of these
model design and analysis options enabled obtaining metabolic and catalytic networks showing several
central features of biological metabolism, some more clearly than in previous models: metabolic
networks with stepwise synthesis, energy coupling, catalysts regulation, SN2 coupling, redox coupling,
intermediate cycling, coupled inverse pathways (metabolic cycling), autocatalytic cycles and catalytic
cascades. The results strongly suggest that the main biological metabolism features, including the
genotype–phenotype interpretation, are caused by the principles of catalytic systems and are prior to
modern genetic systems principles. It also gives further theoretical support to the thesis that the basic
features of biologic metabolism are a consequence of the time evolution of a random catalyst search
working on an open system with a permanent food source. The importance of the food source
characteristics and evolutionary possibilities are discussed.
Proceedings of the 12th Portuguese Conference on Artificial Inteligence, 2005
A computational artificial chemistry (AC) system, called LAC, was developed bearing in mind the m... more A computational artificial chemistry (AC) system, called LAC, was developed bearing in mind the major biochemistry principles. Basic elements may be interpreted as small carbon molecules capable of bonding by nucleophilic substitution or nucleophilic addition. Reactions similar to hydrolysis and oxidation-reduction complete the present set of LAC site interaction rules. Reaction extension is governed by artificial thermodynamic principles and the reaction rate is controlled by specific catalysts made of the same kind of basic elements they act upon. The preliminary results of LAC experiments show the ability to mimic enzyme regulation and oscillatory reactions.
Some of the ideas on this paper were presented at session #1, October 28th 2014 on the meeting "... more Some of the ideas on this paper were presented at session #1, October 28th 2014 on the meeting
" 'What Is Life?' – talks between the sciences and the humanities" celebrating the 70 years of Erwin Schrödinger's "What Is Life?" publication.
Biological carbon chemistry is formalized as a logical system, with a formal language, a grammar ... more Biological carbon chemistry is formalized as a logical system, with a formal language, a grammar and an inference system. The evolution of the language by random application of production rules yields sentence networks containing cycles due to grammar ambiguity. This suggests that any real chemistry that is a model of this type of formal system is able to develop chemical organizations.
The linguistic description is proposed as the centrepiece of scientific modelling, being the way ... more The linguistic description is proposed as the centrepiece of scientific modelling, being the way by which the concepts that are considered relevant to a target system's composition and behaviour are presented, manipulated and communicated. The expression " model prescription " is used to mean the linguistic piece that describes a target system and consequently prescribes the production of synthetic data intended to model physically acquired data. The model prescription is in itself a concept of a target system that uses other systems' concepts, as well as concepts of objects, properties, relations and actions, to describe its structure and behaviour. The communication of a model prescription is therefore dependent on the intersubjective understanding and acceptance of the concepts used. Disentangled and narrower concepts of model and graphics are proposed. " Model " is restricted to representation by the same kind, categorically matched, while representations by different kind are named " graphics ". Data is identified as the sole touching point between physical systems and its human conceptualizations and the use of data-based inference by regression is analysed and some problems identified. Besides logic-mathematical relations, causal relations are an important part of modelling and a strict characterization of causal mechanisms is made based on energy transfers. Modelling examples are given to illustrate the generality of the definitions used as well as some of the problems with scientific modelling.