MANAGEMENT OF AUTISM SPECTRUM DISORDER (ASD) and COLLABORATIVE TEAMS

Autism Spectrum disorder (ASD) is a condition related to the development of the brain that can lead to persistent challenges with socialization, restricted interests, and repeated behaviour. Diagnosis for ASD is used as a basis of DSM-5 (Diagnostic and Statistical Manual of Mental Disorder) produced by American Psychiatric Association. ASD is observed in children during early years of life and significantly affects an individual’s wellbeing. Autism has remained a mystery for many specialists and researchers  for years. Although the cause of autism is still unknown, a number of strategies have been developed that have helped so many people around the world to live independently. So far there are no authentic facts for ASD prevalence in Pakistan however the statistics is roughly calculated from South Asia that ASD might be as common in Pakistan as somewhere else around the world. In a country like Pakistan where Autism is still a new phenomenon especially in rural areas, we have very restricted qualified human resources to provide a reliable rehabilitation service for a child with ASD and their family. Apart from that due to inadequate awareness exposure, knowledge, and incompetency in diagnosis, these children go undiagnosed and are mishandled.

Synthesis, Characterization and Biological Activities of Isocoumarins, Triazoles, Thiadiazoles and Indolinones

The work presented in this thesis consists of the synthesis, characterization, and biological screening of heterocyclic compounds. For convenience, the work has been divided into two parts, part one is related to the compounds containing oxygen atom in the heterocyclic ring whereas part two refers to the compounds containing nitrogen and/ or sulphur atoms in the heterocyclic ring. Part one of this thesis is related to the synthesis, characterization and biological activity of some heterocyclic compounds containing oxygen in the ring. These compounds include some naturally and unnaturally occurring substituted isocoumarins and 3,4-dihydroisocoumarins. The synthesis of naturally occurring isocoumarin Thunberginol B is reported, in which 3,5-dimethoxyhomophthalic acid is a key intermediate for the synthesis of Thunberginol B. It was synthesized efficiently in five steps from 3,5-dimethoxybenzaldehyde via a series of reactions including synthesis of 3,5-dimethoxycinnamic acid, 3-(3′,5′- dimethoxyphenyl)propionic acid, cyclization of 3-(3′,5′-dimethoxyphenyl)propionic acid to 5,7-dimethoxy-1-indanone and oxidative decomposition of methyl 2- hydroxy-2-(5,7-dimethyoxy-1-oxo-1H-inden-2(3H)-ylidene)acetate dimethoxyhomophthalic acid. 3,4-Dimethoxybenzoylchloride from 3,4-dimethoxybenzoic acid condensation with to 3,5- was prepared on reaction with thionyl chloride which on 3,5-dimethoxyhomophthalic acid afforded 3-(3'',4''- dimethoxyphenyl)-6,8-dimethoxyisocoumarin. Complete demethylation of 3-(3'',4''- dimethoxyphenyl)-6,8-dimethoxyisocoumarin with hydrobromic acid in acetic acid gave 3-(3'',4''-dihydroxyphenyl)-6,8-dihydroxyisocoumarin (Thunberginol B). In addition to above, some unnaturally occurring halogenated isocoumarins and their 3,4-dihydrodrivatives were also synthesized. The difluorophenyl- and dichlorophenylisocoumarins by condensation of homophthalic acid with an appropriate acid chloride. Alkaline hydrolysis of the isocoumarins yielded corresponding keto-acids, which on reduction give the corresponding racemichydroxy-acids. 3,4-Dihydroisocoumarins were obtained from these racemic hydroxy-acids by cyclodehydration using acetic anhydride. All the synthesised compounds were identified using their IR, 1 H NMR and mass spectral data. In many cases 13 C NMR and elemental analysis data were employed to support the characterization. In each case, a plasible mass fragmentation pattern is suggested. The synthesized compounds were screened for their antifungal, antibacterial, herbicidal, insecticidal, fungicidal, anti- metastatic, brine shrimp lethality, antioxidant, anti -inflammatory, antiviral, anti- HIV, anti-HBV and anticancer activities and in some cases, very fascinating results were obtained which were then published in different international journals. These synthetic schemes have tremendous potential for further synthesis of novel biological active compounds. Part two of the thesis describes the synthesis and biological screening of some, hitherto unreported, isatin derivatives (Indolinones), 1,4-disubstituted thiosemicarbazides and their related 2,5-disubstituted-1,3,4-thiadiazoles and 4,5- disubstituted-3H-1,2,4-triazole-3-thiones. Indolinones were formed by the direct condensation of hydrazides with halogenated isatins. Triazoles were formed by intramolecular dehydrative cyclization of thiosemicarbazides in basic media while thiadiazoles were formed in acidic media, which is an intermediate during the synthesis of various heterocyclic compounds. Thiosemicarbazides were formed by aldol type condensation reaction of acid hydrazides and isothiocyanates. Isothiocyanates were formed by the reaction of anilines with carbon disulphide in ammonium hydroxide solution to yield ammonium dithiocarbamate, an intermediate which on oxidation with lead nitrate yield isothiocyanate. Acid hydrazides were formed by the reaction of esters of carboxylic acid with hydrazine hydrate and esters were formed by refluxing carboxylic acid in methanol in catalytic amount of carboxylic acids. As a result of these synthetic schemes, thirty new indolinones, ten disubstituted-1,3,4-thiadiazoles and twenty disubstituted 1,2,4-triazole-3-thiones were synthesized. The characterization ofthese synthesized compounds was carried out by IR, 1 H NMR, 13 C NMR, elemental analysis, Mass spectral data and XRD analysis. The synthesized compounds were screened for their antifungal, antibacterial, herbicidal, insecticidal, fungicidal, plant growth regulatory activity and antiviral activities.