یہ زخم اپنے دل کا تو سِل بھی سکتا تھا
تُو کن اگر جو کہتا وہ مل بھی سکتا تھا
پژمردہ سا یہ غنچہ ہم دل ہیں جس کو کہتے
گر ساتھ وہ جو چلتا تو کھل بھی سکتا تھا
The scope of this article is to find out the strengths and weaknesses of M.H. Panhwar’s historical work and to compare it with other scholars of Sindh. He is the initiator of scientific history writing of Sindh and the only historian who tried to uncover the face behind the social organisation of Sindh. According to him, ‘History is the history of production, control over the means of production and production to its final distribution’. The history is more about people than that of the ruling class as people are makers of history. He had vision to analyze things in their correct historical perspective and, in this context, he took support of archeology, as it is the source of scientific truth. Writing history with data acquired through carbon testing is a new phenomenon in Sindh, which was locally introduced by M. H Panhwar.1 M. H. Panhwar, therefore, was one of the pioneers in giving a new meaning to history by including both ruling elites and the common folk, progressive science, crop technology, forest, wildlife, etc.2 He was the first to throw light on areas which were ignored by other historians. According to him, history written before him is full of the accounts of the rulers’ role in relation to their nobles and foes, battles they fought, attacks, palace plotting, mausoleums, folklore, fiction and so on. Accounts regarding contemporary climate, environments, diversion of rivers, courses and the resultant ruination of irrigation systems, migrations, shifting of people, occupations, social life of the populace etc. Found little room in written histories. For instance changes in production and its means, administration and justice, agriculture, land, animal husbandry, irrigation sources and methods of mining, metallurgy, industry and industrial goods, matrimonial institutions, family and children, houses and interiors, art, architecture, archaeology, personal appearance, dresses, ornaments, foods and drinks, taxes, coins and currency, science and technology, foreign contacts, international trades and traders, routes of trades, religious beliefs, philosophy, hygiene, medicine and doctors, superstitions, common citizens, economic conditions, historical geography of bygone ages, classes of work and their relation with one another, household life, customs, entertainments, pastimes, leisure, attitude of man to nature, languages, literature, literary contacts with outside word, learning and thoughts, status of women and children in affluence and extreme poverty.3 Hence, in real sense M.H Panhwar was scholar of Haig’s Raverty’s and Lambrick’s calibre.
The work presented in this thesis has been divided into two parts. Part one deals with the synthesis, characterization and biological activity of some 7-substituted 6,8- dioxygenated isocoumarins and 3,4-dihydroisocoumarins. Chapter one includes general introduction, nomenclature, structural types, biosynthesis, and extensive examples on pharmacological efficacy of isocoumarins and 3,4-dihydroisocoumarins from literature. It also provides some of the most significant synthetic routes and the reactions of isocoumarins and 3,4-dihydroisocoumarins and their interconversion. The total synthesis of structural analogues of some naturally occurring bioactive isocoumarins and dihydroisocoumarins viz. Hiburipyranone, Cytogenin, Montroumarin, Scorzocreticin, Annulatomarin, Thunberginol B, starting from 3,5-dimethoxy-4-methyl homophthalic acid is the subject of Chapter two. The synthesis of 3,5-dimethoxy-4- methylhomophthalic acid from simplest precursor p-toluic acid was carried out. The substituted homophthalic acid was then converted into corresponding anhydride which was then condensed with various acyl and aroyl chlorides to afford the corresponding 3- alkyl or 3-arylisocoumarins. The isocoumarins were then converted into corresponding 3,4-dihydroisocoumarins and the latter were then demethylated to afford corresponding 6,8-dihydroxy-3,4-dihydroisocoumarins. The structures of all of the synthesized compounds were confirmed using FTIR, 1H NMR, 13 C NMR and mass spectral data. Chapter three provides the physical constants and spectroscopic data of the synthesized compounds. Chapter four deals with the biological activities of the compounds synthesized. Antibacterial activity was determined against ten different Gram positive and Gram negative bacterial strains (Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus bulgaricus, Escherichia coli, Klebsiella pneumonae, Pasteurella multocida, Proteus vulgaris, Pseudomonas aeruginosa and Salmonella typhi) using agar well diffusion method. In vitro antimalarial activity was performed against malarial parasite Plasmodium falciparum. The cytotoxic activity of the synthesized compounds was determined against human keratinocyte cell lines. Chapter five depicts total synthesis of a natural product 8-hydroxy-7- hydoxymethyl-6-methoxy-3,4-dihydroisocoumarin (Stellatin) isolated from mycelium of Aspergillus variecolor. The structures of the precursor compounds and the Stellatin were determined by FTIR, NMR and mass spectroscopic data. These compounds were evaluated for their antibacterial activity against ten different gram positive and gram negative bacterial strains. The cytotoxic activity was performed against human keratinocyte cell lines. Part two is related to the synthesis of some 3-(substituted phenyl)isocoumarins, 3- (substituted phenyl)isocoumarin-1-thiones, 3-(substituted phenyl)isoquinolones and some 1-aryl-7,8-dichloroisochromans. Chapter seven, after general introduction, describes the synthesis and biological activity of these compounds. The unsubstituted homophthalic acid was converted into anhydride by treatment with acetic anhydride. The latter was then converted into 3-(substituted phenyl)isocoumarins by reacting it with suitable acid chlorides. The isocoumarins were then converted into corresponding 3-(substituted phenyl)isoquinolones by treatment with formamide. The 3-(substituted phenyl) isocoumarin-1-thiones were synthesized from isocoumarins using Lawesson’s reagent under microwave irradiation. Microwave assisted synthesis of some (±)-1-aryl-7,8- dichloroisochromans was carried out by condensation of 2-(3,4-dimethoxyphenyl) ethanol with a variety of aromatic aldehydes via an acid catalyzed oxa-Pictet-Spengler reaction. All of these synthesized compounds were characterized by IR, 1H, 13C NMR and mass spectroscopic data. In vitro antibacterial activity of these compounds was determined against ten different Gram positive and Gram negative bacterial strains using agar well diffusion method. The comparative analysis of the antibacterial activity of the 3-(substituted phenyl)isocoumarins, 3-(substituted phenyl)isocoumarin-1-thiones and 3-(substituted phenyl)isoquinolones is described. Accordingly, the antibacterial activity increases when isocoumarins were converted into corresponding isocoumarin-1-thiones but decreases on conversion into corresponding isoquinolones.